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1
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Xing Y, Zhou L, Chen Y, Zhang Q, Wu X, Gan Z, Wu K, Jiang D, Wei S, Chen H. A dual-peptides and specific promoter-modified nano gene delivery system for myocardial hypertrophy treatment. Int J Biol Macromol 2025; 311:143759. [PMID: 40319986 DOI: 10.1016/j.ijbiomac.2025.143759] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Revised: 04/15/2025] [Accepted: 04/30/2025] [Indexed: 05/07/2025]
Abstract
Cardiac hypertrophy represents the heart's adaptive response to physiological or pathological stimuli, functioning to alleviate ventricular wall stress and preserve cardiac function and efficiency. However, pathological hypertrophy usually progresses to heart failure. Gene therapy, in contrast to conventional chemotherapeutic drugs, has the ability to impact cardiac hypertrophy directly, while the lack of adequate vectors limits its application. Gemini surfactants (GS) have been proven to be effective for transfection in vivo in earlier research. To diminish the natural liver targeting of GS nanoparticles, a dual-targeted myocardial biomimetic GS nanocomplex gene delivery system with functional peptides TAT and PCM modified and synergized with cardiac-specific promoter chicken cardiac troponin T promoter (cTnT) is designed in this study. Bioluminescence imaging reveals the utility of targeting hypertrophy myocardium, resulting in low localization in the liver upon systemic administration. Biochemical indicators, echocardiography, gross morphology and histology all indicate that GS-nanocomplexes attenuate ISO-induced cardiac hypertrophy. RNA sequencing results reflect different uptake pathways for different GS nanocomplexes, and the investigation of cellular uptake under various endocytosis inhibitors demonstrate that clathrin-mediated endocytosis (CME) serves as the primary endocytic pathway for GS-pDNA uptake and caveolin-mediated endocytosis (CVME) serves as the primary endocytic pathway for GS-pDNA-TP-RBCM uptake. The endocytic pathway for nanocomplexes is confirmed by CAV-1 silencing. In summary, this research presents a dual myocardium-targeted biomimetic GS nanocomplex for gene delivery for cardiomyocytes. The in vivo and in vitro targeting ability, good biocompatibility and helpful therapeutic efficacy for cardiac hypertrophy are verified, and the uptake mechanism and intracellular transport pathway of GS nanocomplex are revealed. This innovative approach provides a promising therapeutic strategy for the treatment of cardiac hypertrophy.
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Affiliation(s)
- Yangchen Xing
- College of Pharmacy, Chongqing Medical University, Yixueyuan Road, Yuzhong District, Chongqing 400016, PR China
| | - Lu Zhou
- College of Pharmacy, Chongqing Medical University, Yixueyuan Road, Yuzhong District, Chongqing 400016, PR China
| | - Yuxin Chen
- College of Pharmacy, Chongqing Medical University, Yixueyuan Road, Yuzhong District, Chongqing 400016, PR China
| | - Qianyu Zhang
- College of Pharmacy, Chongqing Medical University, Yixueyuan Road, Yuzhong District, Chongqing 400016, PR China
| | - Xianwei Wu
- College of Pharmacy, Chongqing Medical University, Yixueyuan Road, Yuzhong District, Chongqing 400016, PR China
| | - Zongjie Gan
- College of Pharmacy, Chongqing Medical University, Yixueyuan Road, Yuzhong District, Chongqing 400016, PR China
| | - Kexin Wu
- College of Pharmacy, Chongqing Medical University, Yixueyuan Road, Yuzhong District, Chongqing 400016, PR China; College of Pharmaceutical Sciences, Zhejiang University, Yuhangtang Road, Xihu District, Hangzhou 310012, PR China
| | - Dongjun Jiang
- College of Pharmacy, Chongqing Medical University, Yixueyuan Road, Yuzhong District, Chongqing 400016, PR China
| | - Shiqi Wei
- College of Pharmacy, Chongqing Medical University, Yixueyuan Road, Yuzhong District, Chongqing 400016, PR China
| | - Huali Chen
- College of Pharmacy, Chongqing Medical University, Yixueyuan Road, Yuzhong District, Chongqing 400016, PR China.
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2
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Zhang C, Zhang L, Chen L, Zheng Y, Zhang S, Guo S, Hu S. Mitigating effects of hydroxysafflor yellow a on atherosclerotic inflammatory responses based on flavonoid macromolecule compound: Inhibition of Piezo1-YAP/JNK protein pathway. Int J Biol Macromol 2025; 309:142961. [PMID: 40220830 DOI: 10.1016/j.ijbiomac.2025.142961] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2025] [Revised: 03/27/2025] [Accepted: 04/06/2025] [Indexed: 04/14/2025]
Abstract
Atherosclerosis (AS) is an important cardiovascular disease caused by inflammation. The inhibitory effect of HysA on the Piezo1-YAP/JNK signaling pathway in a mouse model of AS was studied to clarify its anti-inflammatory effects. The study evaluated HysA's ability to bind Piezo1 through molecular docking analysis. C57BL/6 mice were used to establish AS model, and cell treatment and animal experiments were carried out. Inflammatory markers and lipid accumulation were evaluated using quantitative real-time PCR (qRT-PCR), Westernblot, enzyme-linked immunosorbent assay (ELISA), immunofluorescence, and oil red O staining techniques. Weight changes in mice were recorded to monitor disease progression. The molecular docking results show that HysA has a good binding affinity with Piezo1. In a mouse model of AS, treatment with HysA significantly reduced levels of inflammatory cytokines and inhibited the activation of YAP and JNK signaling pathways. The HysA treatment group showed lower oil red O staining levels, indicating that it effectively mitigated lipid deposition. Therefore, HysA significantly alleviates the inflammatory response of atherosclerosis by inhibiting the Piezo1-YAP/JNK signaling pathway, suggesting its potential application in the prevention and treatment of atherosclerosis.
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Affiliation(s)
- Chunxiao Zhang
- Traditional Chinese Medicine Department, Shaoxing Hospital of Traditional Chinese Medicine, Shaoxing City 312000, Zhejiang Province, China
| | - Lei Zhang
- Internal Medicine Department, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan City 250011, Shandong Province, China
| | - Lanyong Chen
- Clinical College, Zhejiang Chinese Medical University, Hangzhou City 310000, Zhejiang Province, China
| | - Yuhui Zheng
- Traditional Chinese Medicine Department, Shaoxing Hospital of Traditional Chinese Medicine, Shaoxing City 312000, Zhejiang Province, China
| | - Shengyang Zhang
- Traditional Chinese Medicine Department, Shaoxing Hospital of Traditional Chinese Medicine, Shaoxing City 312000, Zhejiang Province, China
| | - Shuren Guo
- Clinical College, Zhejiang Chinese Medical University, Hangzhou City 310000, Zhejiang Province, China
| | - Songfeng Hu
- Traditional Chinese Medicine Department, Shaoxing Hospital of Traditional Chinese Medicine, Shaoxing City 312000, Zhejiang Province, China.
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3
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Wang W, Xu D, Ding J, Pan Y, Wang F, Su S, Peng X, Zhang S, Zhang W. Nanotechnology Innovations in Myocardial Infarction: Diagnosis, Treatment and the Way Forward. J Cardiovasc Transl Res 2025:10.1007/s12265-025-10614-1. [PMID: 40205317 DOI: 10.1007/s12265-025-10614-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Accepted: 03/28/2025] [Indexed: 04/11/2025]
Abstract
Myocardial infarction (MI) is a global health concern that necessitates continued advancements in diagnostic and therapeutic modalities. Nanotechnology facilitates prompt diagnosis and personalized treatment. This manuscript explicitly reviews the application of innovative methodologies for identifying cardiac biomarkers to facilitate the early diagnosis of MI and its clinical management. Nanoscale agents such as nanoparticles and nanosensors have been employed for this purpose. Technological advancements in medical imaging are revolutionizing therapeutic approaches while reducing morbidity and mortality typically associated with cardiac tissue injury. Besides all, applications of nanotechnology in therapeutics have proven extremely effective. The development of nanoparticle-based customized drug delivery systems will contribute to more effective treatments, fewer side effects, and improved therapeutic outcomes. Biomaterials and nanoscale surgical technologies may benefit patients with MI by promoting tissue regeneration and repair. This manuscript also investigates the ethical and legal limitations that could prevent seamless incorporation of nanotechnology into clinical practice.
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Affiliation(s)
- Wenhai Wang
- Department of Cardiology, Jilin Province FAW General Hospital, Changchun, 130000, China
| | - Dexin Xu
- Department of Orthopedics, Jilin Province FAW General Hospital, Changchun, 130000, China
| | - Jian Ding
- Department of Electrodiagnosis, Jilin Province FAW General Hospital, Changchun, 130000, China
| | - Yinping Pan
- Department of Pediatrics, Jilin Province FAW General Hospital, Changchun, 130000, China
| | - Fang Wang
- Department of Cardiology, Jilin Province FAW General Hospital, Changchun, 130000, China
| | - Shu Su
- Department of Medical Laboratory, Jilin Province FAW General Hospital, Changchun, 130000, China
| | - Xia Peng
- Department of Cardiology, Jilin Province FAW General Hospital, Changchun, 130000, China
| | - Shitong Zhang
- Department of Neurology I, Qian Wei Hospital of Jilin Province, Changchun, 130012, China
| | - Wenbin Zhang
- Department of Cardiology, Jilin Province FAW General Hospital, Changchun, 130000, China.
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Zhou Q, Wang Y, Si G, Chen X, Mu D, Zhang B. Application of Nanomaterials in Early Imaging and Advanced Treatment of Atherosclerosis. CHEMICAL & BIOMEDICAL IMAGING 2025; 3:51-76. [PMID: 40018650 PMCID: PMC11863161 DOI: 10.1021/cbmi.4c00064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Revised: 11/26/2024] [Accepted: 11/26/2024] [Indexed: 03/01/2025]
Abstract
Atherosclerosis (AS) is a serious disease that poses a significant threat to the global population. In this review, we analyze the development of AS from multiple perspectives, aiming to elucidate its molecular mechanisms. We also focus on imaging techniques and therapeutic approaches, highlighting the crucial role of nanomaterials in both imaging and therapy for AS. By leveraging their compatibility and targeting capabilities, nanomaterials can be integrated with traditional medical imaging and therapeutic agents to achieve targeted drug delivery, controlled release, and precise localization and imaging of atherosclerotic plaques.
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Affiliation(s)
- Qianru Zhou
- Department
of Radiology, Nanjing Drum Tower Hospital Clinical College of Traditional
Chinese and Western Medicine, Nanjing University
of Chinese Medicine, Nanjing 210008, China
| | - Yujie Wang
- Department
of Radiology, Nanjing Drum Tower Hospital
Clinical College of Jiangsu University, Nanjing 210008, China
| | - Guangxiang Si
- Jiangsu
Key Laboratory for Biomaterials and Devices, School of Biological
Science and Medical Engineering, Southeast
University, Nanjing 210000, China
| | - Xingbiao Chen
- Clinical
Science, Philips Healthcare, Shanghai 200233, China
| | - Dan Mu
- Department
of Radiology, Nanjing Drum Tower Hospital, Affiliated Hospital of
Medical School, Nanjing University, No. 321 Zhongshan Road, Nanjing 210008, China
| | - Bing Zhang
- Department
of Radiology, Nanjing Drum Tower Hospital, Affiliated Hospital of
Medical School, Nanjing University, No. 321 Zhongshan Road, Nanjing 210008, China
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5
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Sharma I, Bhardwaj S, Karwasra R, Kaushik D, Sharma S. The Emergence of Nanotechnology in the Prognosis and Treatment of Myocardial Infarctions. RECENT PATENTS ON NANOTECHNOLOGY 2025; 19:35-55. [PMID: 37904554 DOI: 10.2174/1872210517666230721123453] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Revised: 06/08/2023] [Accepted: 06/16/2023] [Indexed: 11/01/2023]
Abstract
Myocardial infarction (MI), commonly known as a heart attack, is a critical cardiovascular condition associated with high morbidity and mortality rates worldwide. Despite significant advancements in traditional treatment modalities, there remains a need for innovative approaches to improve the prognosis and treatment outcomes of MI. The emergence of nanotechnology has provided a promising avenue for revolutionizing the management of this life-threatening condition. This manuscript aims to explore the role of nanotechnology in the prognosis and treatment of myocardial infarctions. Nanotechnology offers unique advantages in the field of cardiovascular medicine, including targeted drug delivery, precise imaging and diagnosis, regenerative medicine approaches, biosensors and monitoring, and the integration of therapy and diagnostics (theragnostic). One of the key advantages of nanotechnology is the ability to deliver therapeutic agents directly to the affected site. Nanoparticles can be engineered to carry drugs specifically to damaged heart tissue, enhancing their efficacy while minimizing off-target effects. Additionally, nanoparticles can serve as contrast agents, facilitating high-resolution imaging and accurate diagnosis of infarcted heart tissue. Furthermore, nanotechnology-based regenerative approaches show promise in promoting tissue healing and regeneration after MI. Nanomaterials can provide scaffolding structures or release growth factors to stimulate the growth of new blood vessels and support tissue repair. This regenerative potential holds significant implications for restoring cardiac function and minimizing long-term complications. Nanotechnology also enables real-time monitoring of critical parameters within the heart, such as oxygen levels, pH, and electrical activity, through the utilization of nanoscale devices and sensors. This capability allows for the early detection of complications and facilitates timely interventions. Moreover, the integration of therapy and diagnostics through nanotechnology- based platforms, known as theragnostic, holds tremendous potential. Nanoparticles can simultaneously deliver therapeutic agents while providing imaging capabilities, enabling personalized treatment strategies tailored to individual patients. This manuscript will review the recent advancements, clinical trials, and patents in nanotechnology for the prognosis and treatment of myocardial infarctions. By leveraging nanotechnology's unique properties and applications, researchers and clinicians can develop innovative therapeutic approaches that enhance patient outcomes, improve prognosis, and ultimately revolutionize the management of myocardial infarctions.
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Affiliation(s)
- Isha Sharma
- Department of Pharmaceutical Sciences, Gurugram University, Gurugram, 122018, India
| | - Shivani Bhardwaj
- ICAR- Central Institute for Research on Buffaloes Hisar, Haryana, 125001, India
| | - Ritu Karwasra
- Central Council for Research in Unani Medicine, Ministry of Ayush, Govt. of India, New Delhi, 110058, India
| | - Dhirender Kaushik
- Department of Pharmaceutical Sciences, Gurugram University, Gurugram, 122018, India
| | - Shivkant Sharma
- Department of Pharmaceutical Sciences, Gurugram University, Gurugram, 122018, India
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6
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Sun X, Tian T, Lian Y, Cui Z. Current Advances in Viral Nanoparticles for Biomedicine. ACS NANO 2024; 18:33827-33863. [PMID: 39648920 DOI: 10.1021/acsnano.4c13146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/10/2024]
Abstract
Viral nanoparticles (VNPs) have emerged as crucial tools in the field of biomedicine. Leveraging their biological and physicochemical properties, VNPs exhibit significant advantages in the prevention, diagnosis, and treatment of human diseases. Through techniques such as chemical bioconjugation, infusion, genetic engineering, and encapsulation, these VNPs have been endowed with multifunctional capabilities, including the display of functional peptides or proteins, encapsulation of therapeutic drugs or inorganic particles, integration with imaging agents, and conjugation with bioactive molecules. This review provides an in-depth analysis of VNPs in biomedicine, elucidating their diverse types, distinctive features, production methods, and complex design principles behind multifunctional VNPs. It highlights recent innovative research and various applications, covering their roles in imaging, drug delivery, therapeutics, gene delivery, vaccines, immunotherapy, and tissue regeneration. Additionally, the review provides an assessment of their safety and biocompatibility and discusses challenges and future opportunities in the field, underscoring the vast potential and evolving nature of VNP research.
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Affiliation(s)
- Xianxun Sun
- School of Life Sciences, Jianghan University, Wuhan 430056, China
| | - Tao Tian
- School of Life Sciences, Jianghan University, Wuhan 430056, China
- State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China
| | - Yindong Lian
- School of Life Sciences, Jianghan University, Wuhan 430056, China
- State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China
| | - Zongqiang Cui
- State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China
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7
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Li R, Xu A, Chen Y, Li Y, Fu R, Jiang W, Li X. Fabrication of apigenin and adenosine-loaded nanoparticles against doxorubicin-induced myocardial infarction by reducing inflammation and oxidative stress. BMC Biotechnol 2024; 24:87. [PMID: 39501266 PMCID: PMC11539433 DOI: 10.1186/s12896-024-00912-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Accepted: 10/10/2024] [Indexed: 11/08/2024] Open
Abstract
The study's goals are to fabricate PLGA nanoparticles (PNPs) loaded with apigenin (AP) and adenosine (AD) using a microfluidic preparation method to a standard emulsification method and investigate the possible heart-protective effects of AP-AD PNPs made using the emulsification method. Compared to microfluidics, the emulsification method fabricated small-size nanoparticles, which are better at encapsulating drugs, retaining more drugs, and having a low viscosity for the myocardial infarction (MI) injection. TheMI model was developed using SD rats injected under the skin with 85 mg/kg doxorubicin (DOX) for 2 days. The metabolic results showed that our AP-AD PNPs accelerated the blood flow in rats with MI, which increased the amounts of AP and AD in the circulatory system. This led to significant improvements in the cardiac index and lower amounts of AST, LDH, and CK in the blood. A histopathological study using Hematoxylin&eosin, and TUNEL staining showed that cardiac function had improved and apoptosis had decreased. Moreover, tests that checked the amounts of IL-6, TNF-α, NO, GSH, MDA, and SOD showed that AP-AD PNPs may help treat MI by reducing oxidative stress and inflammation, making it a potentially useful therapeutic approach.
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Affiliation(s)
- Ruixuan Li
- Department of Cardiology, The Third Xiangya Hospital of Central South University, Changsha, 410013, China
| | - Aixia Xu
- Department of Endocrinology, Changsha Central Hospital, Changsha, 410007, China
| | - Ye Chen
- Department of Cardiology, The Third Xiangya Hospital of Central South University, Changsha, 410013, China
| | - Yihui Li
- Department of Cardiology, The Third Xiangya Hospital of Central South University, Changsha, 410013, China
| | - Ru Fu
- Department of Cardiology, The Third Xiangya Hospital of Central South University, Changsha, 410013, China
| | - Weihong Jiang
- Department of Cardiology, The Third Xiangya Hospital of Central South University, Changsha, 410013, China.
| | - Xiaogang Li
- Department of Cardiology, The Third Xiangya Hospital of Central South University, Changsha, 410013, China.
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Lin Y, Liu J, Chong SY, Ting HJ, Tang X, Yang L, Zhang S, Qi X, Pei P, Yi Z, Huang C, Hou X, Gao L, Torta F, Liu X, Liu B, Kah JCY, Wang J. Dual-Function Nanoscale Coordination Polymer Nanoparticles for Targeted Diagnosis and Therapeutic Delivery in Atherosclerosis. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2024; 20:e2401659. [PMID: 39185808 PMCID: PMC11579969 DOI: 10.1002/smll.202401659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/03/2024] [Revised: 08/08/2024] [Indexed: 08/27/2024]
Abstract
Atherosclerosis is the primary cause of cardiovascular events such as heart attacks and strokes. However, current medical practice lacks non-invasive, reliable approaches for both imaging atherosclerotic plaques and delivering therapeutic agents directly therein. Here, a biocompatible and biodegradable pH-responsive nanoscale coordination polymers (NCPs) based theranostic system is reported for managing atherosclerosis. NCPs are synthesized with a pH-responsive benzoic-imine (BI) linker and Gd3+. Simvastatin (ST), a statin not used for lowering blood cholesterol but known for its anti-inflammatory and antioxidant effects in mice, is chosen as the model drug. By incorporating ST into the hydrophobic domain of a lipid bilayer shell on NCPs surfaces, ST/NCP-PEG nanoparticles are created that are designed for dual purposes: they diagnose and treat atherosclerosis. When administered intravenously, they target atherosclerotic plaques, breaking down in the mild acidic microenvironment of the plaque to release ST, which reduces inflammation and oxidative stress, and Gd-complexes for MR imaging of the plaques. ST/NCP-PEG nanoparticles show efficacy in slowing the progression of atherosclerosis in live models and allow for simultaneous in vivo monitoring without observed toxicity in major organs. This positions ST/NCP-PEG nanoparticles as a promising strategy for the spontaneous diagnosis and treatment of atherosclerosis.
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Affiliation(s)
- Yuanzhe Lin
- Department of SurgeryYong Loo Lin School of MedicineNational University of Singapore1E Kent Ridge RdSingapore119228Singapore
- Department of Biomedical EngineeringNational University of Singapore4 Engineering Drive 3, Block E4, #04‐08Singapore117583Singapore
- Nanomedicine Translational Research ProgramYong Loo Lin School of MedicineNational University of SingaporeSingapore117609Singapore
| | - Jingjing Liu
- Institute of Translational MedicineMedical CollegeYangzhou UniversityYangzhouJiangsu225001China
- Department of Chemical and Biomolecular EngineeringNational University of SingaporeSingapore117585Singapore
| | - Suet Yen Chong
- Department of SurgeryYong Loo Lin School of MedicineNational University of Singapore1E Kent Ridge RdSingapore119228Singapore
- Nanomedicine Translational Research ProgramYong Loo Lin School of MedicineNational University of SingaporeSingapore117609Singapore
- Cardiovascular Research InstituteNational University Heart Centre Singapore (NUHCS)14 Medical DriveSingapore117599Singapore
| | - Hui Jun Ting
- Department of SurgeryYong Loo Lin School of MedicineNational University of Singapore1E Kent Ridge RdSingapore119228Singapore
- Nanomedicine Translational Research ProgramYong Loo Lin School of MedicineNational University of SingaporeSingapore117609Singapore
| | - Xichuan Tang
- Department of SurgeryYong Loo Lin School of MedicineNational University of Singapore1E Kent Ridge RdSingapore119228Singapore
- Nanomedicine Translational Research ProgramYong Loo Lin School of MedicineNational University of SingaporeSingapore117609Singapore
| | - Liqiang Yang
- Department of SurgeryYong Loo Lin School of MedicineNational University of Singapore1E Kent Ridge RdSingapore119228Singapore
- Nanomedicine Translational Research ProgramYong Loo Lin School of MedicineNational University of SingaporeSingapore117609Singapore
| | - Sitong Zhang
- Department of SurgeryYong Loo Lin School of MedicineNational University of Singapore1E Kent Ridge RdSingapore119228Singapore
- Nanomedicine Translational Research ProgramYong Loo Lin School of MedicineNational University of SingaporeSingapore117609Singapore
| | - Xinyi Qi
- Department of SurgeryYong Loo Lin School of MedicineNational University of Singapore1E Kent Ridge RdSingapore119228Singapore
- Nanomedicine Translational Research ProgramYong Loo Lin School of MedicineNational University of SingaporeSingapore117609Singapore
| | - Peng Pei
- Department of SurgeryYong Loo Lin School of MedicineNational University of Singapore1E Kent Ridge RdSingapore119228Singapore
- Nanomedicine Translational Research ProgramYong Loo Lin School of MedicineNational University of SingaporeSingapore117609Singapore
- Department of ChemistryNational University of Singapore3 Science Drive 3Singapore117543Singapore
| | - Zhigao Yi
- Department of ChemistryNational University of Singapore3 Science Drive 3Singapore117543Singapore
| | - Chenyuan Huang
- Department of SurgeryYong Loo Lin School of MedicineNational University of Singapore1E Kent Ridge RdSingapore119228Singapore
- Nanomedicine Translational Research ProgramYong Loo Lin School of MedicineNational University of SingaporeSingapore117609Singapore
| | - Xiao Hou
- Department of SurgeryYong Loo Lin School of MedicineNational University of Singapore1E Kent Ridge RdSingapore119228Singapore
- Nanomedicine Translational Research ProgramYong Loo Lin School of MedicineNational University of SingaporeSingapore117609Singapore
| | - Liang Gao
- Department of BiochemistryYong Loo Lin School of MedicineNational University of SingaporeSingapore117596Singapore
- Singapore Lipidomics Incubator (SLING)Life Sciences InstituteNational University of SingaporeSingapore117456Singapore
| | - Federico Torta
- Department of BiochemistryYong Loo Lin School of MedicineNational University of SingaporeSingapore117596Singapore
- Singapore Lipidomics Incubator (SLING)Life Sciences InstituteNational University of SingaporeSingapore117456Singapore
| | - Xiaogang Liu
- Department of ChemistryNational University of Singapore3 Science Drive 3Singapore117543Singapore
| | - Bin Liu
- Department of Chemical and Biomolecular EngineeringNational University of SingaporeSingapore117585Singapore
| | - James Chen Yong Kah
- Department of Biomedical EngineeringNational University of Singapore4 Engineering Drive 3, Block E4, #04‐08Singapore117583Singapore
| | - Jiong‐Wei Wang
- Department of SurgeryYong Loo Lin School of MedicineNational University of Singapore1E Kent Ridge RdSingapore119228Singapore
- Nanomedicine Translational Research ProgramYong Loo Lin School of MedicineNational University of SingaporeSingapore117609Singapore
- Cardiovascular Research InstituteNational University Heart Centre Singapore (NUHCS)14 Medical DriveSingapore117599Singapore
- Department of PhysiologyYong Loo Lin School of MedicineNational University of Singapore2 Medical DriveSingapore117593Singapore
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Tong J, Wang Z, Zhang J, Gao R, Liu X, Liao Y, Guo X, Wei Y. Advanced Applications of Nanomaterials in Atherosclerosis Diagnosis and Treatment: Challenges and Future Prospects. ACS APPLIED MATERIALS & INTERFACES 2024; 16:58072-58099. [PMID: 39432384 DOI: 10.1021/acsami.4c13607] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/23/2024]
Abstract
Atherosclerosis-induced coronary artery disease is a major cause of cardiovascular mortality. Clinically, conservative treatment strategies for atherosclerosis still focus on lifestyle interventions and the use of lipid-lowering and anticoagulant medications. Despite achieving some therapeutic effects, these approaches are limited by low bioavailability, long intervention periods, and significant side effects. With the advancement of nanotechnology, nanomaterials have demonstrated extraordinary potential in the biomedical field. Their excellent biocompatibility, surface modifiability, and high targeting capability not only enable efficient diagnosis of plaque progression but also allow precise drug delivery within atherosclerotic plaques, significantly enhancing drug bioavailability and reducing systemic side effects. Here, we systematically review the current research progress of nanomaterials in the field of atherosclerosis to summarize not only the types of nanomaterials but also their applications in both the diagnosis and treatment of atherosclerosis. Notably, in the context of plaque therapy, we provide a comprehensive overview of current nanomaterial applications based on their targeted therapeutic systems for different cell types within plaques. Additionally, we address the persistent challenge of clinical translation of nanomaterials by summarizing current issues and providing directions for innovation and improvement in nanomaterial design. Overall, we believe that this review systematically summarizes the applications and challenges of biomedical nanomaterials in atherosclerosis diagnosis and therapy, thereby offering insights and references for the development of therapeutic materials for atherosclerosis.
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Affiliation(s)
- Junran Tong
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Engineering Research Center for Immunological Diagnosis and Therapy of Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Zhiwen Wang
- Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Jiahui Zhang
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Engineering Research Center for Immunological Diagnosis and Therapy of Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Ran Gao
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Engineering Research Center for Immunological Diagnosis and Therapy of Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Xiangfei Liu
- Department of Cardiology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, 100005, China
| | - Yuhan Liao
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Engineering Research Center for Immunological Diagnosis and Therapy of Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Xiaopeng Guo
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Yumiao Wei
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Engineering Research Center for Immunological Diagnosis and Therapy of Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
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10
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Chaiter Y, Fink DL, Machluf Y. Vascular medicine in the 21 st century: Embracing comprehensive vasculature evaluation and multidisciplinary treatment. World J Clin Cases 2024; 12:6032-6044. [PMID: 39328850 PMCID: PMC11326099 DOI: 10.12998/wjcc.v12.i27.6032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 06/25/2024] [Accepted: 07/10/2024] [Indexed: 07/29/2024] Open
Abstract
The field of vascular medicine has undergone a profound transformation in the 21st century, transforming our approach to assessment and treatment. Atherosclerosis, a complex inflammatory disease that affects medium and large arteries, presents a major challenge for researchers and healthcare professionals. This condition, characterized by arterial plaque formation and narrowing, poses substantial challenges to vascular health at individual, national, and global scales. Its repercussions are far-reaching, with clinical outcomes including ischemic heart disease, ischemic stroke, and peripheral arterial disease-conditions with escalating global prevalence. Early detection of vascular changes caused by atherosclerosis is crucial in preventing these conditions, reducing morbidity, and averting mortality. This article underscored the imperative of adopting a holistic approach to grappling with the intricacies, trajectories, and ramifications of atherosclerosis. It stresses the need for a thorough evaluation of the vasculature and the implementation of a multidisciplinary treatment approach. By considering the entire vascular system, healthcare providers can explore avenues for prevention, early detection, and effective management of this condition, ultimately leading to improved patient outcomes. We discussed current practices and proposed new directions made possible by emerging diagnostic modalities and treatment strategies. Additionally, we considered healthcare expenditure, resource allocation, and the transformative potential of new innovative treatments and technologies.
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Affiliation(s)
- Yoram Chaiter
- The Israeli Center for Emerging Technologies in Hospitals and Hospital-Based Health Technology Assessment, Shamir (Assaf Harofeh) Medical Center, Zerifin 7030100, Israel
| | - Daniel Lyon Fink
- Department of Pediatric Cardiology Unit, HaEmek Medical Center, Afula 1834111, Israel
| | - Yossy Machluf
- Shamir Research Institute, University of Haifa, Kazerin 1290000, Israel
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11
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Wang J, Zhang H, Wan W, Yang H, Zhao J. Advances in nanotechnological approaches for the detection of early markers associated with severe cardiac ailments. Nanomedicine (Lond) 2024; 19:1487-1506. [PMID: 39121377 PMCID: PMC11318751 DOI: 10.1080/17435889.2024.2364581] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Accepted: 05/31/2024] [Indexed: 08/11/2024] Open
Abstract
Mortality from cardiovascular disease (CVD) accounts for over 30% of all deaths globally, necessitating reliable diagnostic tools. Prompt identification and precise diagnosis are critical for effective personalized treatment. Nanotechnology offers promising applications in diagnostics, biosensing and drug delivery for prevalent cardiovascular diseases. Its integration into cardiovascular care enhances diagnostic accuracy, enabling early intervention and tailored treatment plans. By leveraging nanoscale innovations, healthcare professionals can address the complexities of CVD progression and customize interventions based on individual patient needs. Ongoing advancements in nanotechnology continue to shape the landscape of cardiovascular medicine, offering potential for improved patient outcomes and reduced mortality rates from these pervasive diseases.
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Affiliation(s)
- Jie Wang
- Department of Cardiac Care Unit, Yantaishan Hospital, Yantai, Shandong, 264003, China
| | - Haifeng Zhang
- Department of Cardiology, Yantai Yeda Hospital, Yantai, Shangdong, 264006, China
| | - Weiping Wan
- Department of Ultrasound, Yantaishan Hospital, Yantai, Shandong, 264003, China
| | - Haijiao Yang
- Department of Cardiac Care Unit, Yantaishan Hospital, Yantai, Shandong, 264003, China
| | - Jing Zhao
- Department of Critical Care Medicine, Yantaishan Hospital, Yantai, Shandong, 264003, China
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12
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Pang ASR, Dinesh T, Pang NYL, Dinesh V, Pang KYL, Yong CL, Lee SJJ, Yip GW, Bay BH, Srinivasan DK. Nanoparticles as Drug Delivery Systems for the Targeted Treatment of Atherosclerosis. Molecules 2024; 29:2873. [PMID: 38930939 PMCID: PMC11206617 DOI: 10.3390/molecules29122873] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2024] [Revised: 06/03/2024] [Accepted: 06/10/2024] [Indexed: 06/28/2024] Open
Abstract
Atherosclerosis continues to be a leading cause of morbidity and mortality globally. The precise evaluation of the extent of an atherosclerotic plaque is essential for forecasting its likelihood of causing health concerns and tracking treatment outcomes. When compared to conventional methods used, nanoparticles offer clear benefits and excellent development opportunities for the detection and characterisation of susceptible atherosclerotic plaques. In this review, we analyse the recent advancements of nanoparticles as theranostics in the management of atherosclerosis, with an emphasis on applications in drug delivery. Furthermore, the main issues that must be resolved in order to advance clinical utility and future developments of NP research are discussed. It is anticipated that medical NPs will develop into complex and advanced next-generation nanobotics that can carry out a variety of functions in the bloodstream.
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Affiliation(s)
- Alexander Shao-Rong Pang
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; (A.S.-R.P.); (N.Y.-L.P.); (C.L.Y.)
| | - Tarini Dinesh
- Department of Medicine, Government Kilpauk Medical College, Chennai 600010, Tamilnadu, India;
| | - Natalie Yan-Lin Pang
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; (A.S.-R.P.); (N.Y.-L.P.); (C.L.Y.)
| | - Vishalli Dinesh
- Department of Pathology, Dhanalakshmi Srinivasan Medical College Hospital, Perambalur 621113, Tamilnadu, India;
| | - Kimberley Yun-Lin Pang
- Division of Medicine, South Australia Health, Northern Adelaide Local Health Network, Adelaide, SA 5112, Australia; (K.Y.-L.P.); (S.J.J.L.)
| | - Cai Ling Yong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; (A.S.-R.P.); (N.Y.-L.P.); (C.L.Y.)
| | - Shawn Jia Jun Lee
- Division of Medicine, South Australia Health, Northern Adelaide Local Health Network, Adelaide, SA 5112, Australia; (K.Y.-L.P.); (S.J.J.L.)
| | - George W. Yip
- Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117594, Singapore; (G.W.Y.); (B.H.B.)
| | - Boon Huat Bay
- Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117594, Singapore; (G.W.Y.); (B.H.B.)
| | - Dinesh Kumar Srinivasan
- Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117594, Singapore; (G.W.Y.); (B.H.B.)
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13
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Liu Y, Jiang Z, Yang X, Wang Y, Yang B, Fu Q. Engineering Nanoplatforms for Theranostics of Atherosclerotic Plaques. Adv Healthc Mater 2024; 13:e2303612. [PMID: 38564883 DOI: 10.1002/adhm.202303612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Revised: 03/28/2024] [Indexed: 04/04/2024]
Abstract
Atherosclerotic plaque formation is considered the primary pathological mechanism underlying atherosclerotic cardiovascular diseases, leading to severe cardiovascular events such as stroke, acute coronary syndromes, and even sudden cardiac death. Early detection and timely intervention of plaques are challenging due to the lack of typical symptoms in the initial stages. Therefore, precise early detection and intervention play a crucial role in risk stratification of atherosclerotic plaques and achieving favorable post-interventional outcomes. The continuously advancing nanoplatforms have demonstrated numerous advantages including high signal-to-noise ratio, enhanced bioavailability, and specific targeting capabilities for imaging agents and therapeutic drugs, enabling effective visualization and management of atherosclerotic plaques. Motivated by these superior properties, various noninvasive imaging modalities for early recognition of plaques in the preliminary stage of atherosclerosis are comprehensively summarized. Additionally, several therapeutic strategies are proposed to enhance the efficacy of treating atherosclerotic plaques. Finally, existing challenges and promising prospects for accelerating clinical translation of nanoplatform-based molecular imaging and therapy for atherosclerotic plaques are discussed. In conclusion, this review provides an insightful perspective on the diagnosis and therapy of atherosclerotic plaques.
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Affiliation(s)
- Yuying Liu
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao, 266021, China
- Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China
| | - Zeyu Jiang
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao, 266021, China
- Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China
| | - Xiao Yang
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao, 266021, China
| | - Yin Wang
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao, 266021, China
| | - Bin Yang
- Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China
| | - Qinrui Fu
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao, 266021, China
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14
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Bonde S, Osmani RAM, Trivedi R, Patravale V, Angolkar M, Prasad AG, Ravikumar AA. Harnessing DNA origami's therapeutic potential for revolutionizing cardiovascular disease treatment: A comprehensive review. Int J Biol Macromol 2024; 270:132246. [PMID: 38735608 DOI: 10.1016/j.ijbiomac.2024.132246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Revised: 03/25/2024] [Accepted: 05/07/2024] [Indexed: 05/14/2024]
Abstract
DNA origami is a cutting-edge nanotechnology approach that creates precise and detailed 2D and 3D nanostructures. The crucial feature of DNA origami is how it is created, which enables precise control over its size and shape. Biocompatibility, targetability, programmability, and stability are further advantages that make it a potentially beneficial technique for a variety of applications. The preclinical studies of sophisticated programmable nanomedicines and nanodevices that can precisely respond to particular disease-associated triggers and microenvironments have been made possible by recent developments in DNA origami. These stimuli, which are endogenous to the targeted disorders, include protein upregulation, pH, redox status, and small chemicals. Oncology has traditionally been the focus of the majority of past and current research on this subject. Therefore, in this comprehensive review, we delve into the intricate world of DNA origami, exploring its defining features and capabilities. This review covers the fundamental characteristics of DNA origami, targeting DNA origami to cells, cellular uptake, and subcellular localization. Throughout the review, we emphasised on elucidating the imperative for such a therapeutic platform, especially in addressing the complexities of cardiovascular disease (CVD). Moreover, we explore the vast potential inherent in DNA origami technology, envisioning its promising role in the realm of CVD treatment and beyond.
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Affiliation(s)
- Smita Bonde
- Department of Pharmaceutics, SSR College of Pharmacy, Silvassa 396230, UT of Dadra and Nagar Haveli, India.
| | - Riyaz Ali M Osmani
- Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research (JSS AHER), Mysuru 570015, Karnataka, India.
| | - Rashmi Trivedi
- Department of Pharmaceutics, Smt. Kishoritai Bhoyar College of Pharmacy, Kamptee, Nagpur 441002, Maharashtra, India.
| | - Vandana Patravale
- Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Nathalal Parekh Marg, Matunga (E), Mumbai 400019, Maharashtra, India.
| | - Mohit Angolkar
- Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research (JSS AHER), Mysuru 570015, Karnataka, India.
| | - Aprameya Ganesh Prasad
- Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
| | - Akhila Akkihebbal Ravikumar
- Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research (JSS AHER), Mysuru 570015, Karnataka, India.
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15
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Wei Q, Xiao Y, Du L, Li Y. Advances in Nanoparticles in the Prevention and Treatment of Myocardial Infarction. Molecules 2024; 29:2415. [PMID: 38893291 PMCID: PMC11173599 DOI: 10.3390/molecules29112415] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Revised: 05/17/2024] [Accepted: 05/17/2024] [Indexed: 06/21/2024] Open
Abstract
Myocardial infarction (MI) is one of the most prevalent types of cardiovascular disease. During MI, myocardial cells become ischemic and necrotic due to inadequate blood perfusion, leading to irreversible damage to the heart. Despite the development of therapeutic strategies for the prevention and treatment of MI, their effects are still unsatisfactory. Nanoparticles represent a new strategy for the pre-treatment and treatment of MI, and novel multifunctional nanoparticles with preventive and therapeutic capabilities hold promise for the prevention and treatment of this disease. This review summarizes the common types and properties of nanoparticles, and focuses on the research progress of nanoparticles for the prevention and treatment of MI.
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Affiliation(s)
| | | | | | - Ya Li
- College of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China; (Q.W.); (Y.X.); (L.D.)
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16
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De Meyer GRY, Zurek M, Puylaert P, Martinet W. Programmed death of macrophages in atherosclerosis: mechanisms and therapeutic targets. Nat Rev Cardiol 2024; 21:312-325. [PMID: 38163815 DOI: 10.1038/s41569-023-00957-0] [Citation(s) in RCA: 53] [Impact Index Per Article: 53.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/02/2023] [Indexed: 01/03/2024]
Abstract
Atherosclerosis is a progressive inflammatory disorder of the arterial vessel wall characterized by substantial infiltration of macrophages, which exert both favourable and detrimental functions. Early in atherogenesis, macrophages can clear cytotoxic lipoproteins and dead cells, preventing cytotoxicity. Efferocytosis - the efficient clearance of dead cells by macrophages - is crucial for preventing secondary necrosis and stimulating the release of anti-inflammatory cytokines. In addition, macrophages can promote tissue repair and proliferation of vascular smooth muscle cells, thereby increasing plaque stability. However, advanced atherosclerotic plaques contain large numbers of pro-inflammatory macrophages that secrete matrix-degrading enzymes, induce death in surrounding cells and contribute to plaque destabilization and rupture. Importantly, macrophages in the plaque can undergo apoptosis and several forms of regulated necrosis, including necroptosis, pyroptosis and ferroptosis. Regulated necrosis has an important role in the formation and expansion of the necrotic core during plaque progression, and several triggers for necrosis are present within atherosclerotic plaques. This Review focuses on the various forms of programmed macrophage death in atherosclerosis and the pharmacological interventions that target them as a potential means of stabilizing vulnerable plaques and improving the efficacy of currently available anti-atherosclerotic therapies.
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Affiliation(s)
- Guido R Y De Meyer
- Laboratory of Physiopharmacology, University of Antwerp, Antwerp, Belgium.
| | - Michelle Zurek
- Laboratory of Physiopharmacology, University of Antwerp, Antwerp, Belgium
| | - Pauline Puylaert
- Laboratory of Physiopharmacology, University of Antwerp, Antwerp, Belgium
| | - Wim Martinet
- Laboratory of Physiopharmacology, University of Antwerp, Antwerp, Belgium
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17
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Reddy RV, Buchanan L, Swayze A, Fleischmann B, Ghomeshi A, Mondesir RF, Donnenfeld SR, Golan R, Ramasamy R. Rubin H. Flocks (1906-1975): President of American Board of Urology, Chair of Department of Urology at the University of Iowa Carver College of Medicine, and Inventor of Colloidal Gold Therapy for Cancer. Urology 2024:S0090-4295(24)00152-3. [PMID: 38490278 DOI: 10.1016/j.urology.2024.03.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Revised: 01/19/2024] [Accepted: 03/06/2024] [Indexed: 03/17/2024]
Affiliation(s)
- Raghuram V Reddy
- Herbert Wertheim College of Medicine, Florida International University, Miami, FL; Desai Sethi Urology Institute, Miller School of Medicine, University of Miami, Miami, FL.
| | - Logan Buchanan
- University of Tennessee Health Science Center, Memphis, TN; Desai Sethi Urology Institute, Miller School of Medicine, University of Miami, Miami, FL
| | - Aden Swayze
- Herbert Wertheim College of Medicine, Florida International University, Miami, FL; Desai Sethi Urology Institute, Miller School of Medicine, University of Miami, Miami, FL
| | - Benjamin Fleischmann
- Herbert Wertheim College of Medicine, Florida International University, Miami, FL; Desai Sethi Urology Institute, Miller School of Medicine, University of Miami, Miami, FL
| | - Armin Ghomeshi
- Herbert Wertheim College of Medicine, Florida International University, Miami, FL; Desai Sethi Urology Institute, Miller School of Medicine, University of Miami, Miami, FL
| | - Ronscardy F Mondesir
- Herbert Wertheim College of Medicine, Florida International University, Miami, FL; Desai Sethi Urology Institute, Miller School of Medicine, University of Miami, Miami, FL
| | | | - Roei Golan
- Department of Clinical Sciences, Florida State University College of Medicine, Tallahassee, FL; Desai Sethi Urology Institute, Miller School of Medicine, University of Miami, Miami, FL
| | - Ranjith Ramasamy
- Desai Sethi Urology Institute, Miller School of Medicine, University of Miami, Miami, FL
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18
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Ye T, Chen C, Wang D, Huang C, Yan Z, Chen Y, Jin X, Wang X, Ding X, Shen C. Protective effects of Pt-N-C single-atom nanozymes against myocardial ischemia-reperfusion injury. Nat Commun 2024; 15:1682. [PMID: 38396113 PMCID: PMC10891101 DOI: 10.1038/s41467-024-45927-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Accepted: 02/07/2024] [Indexed: 02/25/2024] Open
Abstract
Effective therapeutic strategies for myocardial ischemia/reperfusion (I/R) injury remain elusive. Targeting reactive oxygen species (ROS) provides a practical approach to mitigate myocardial damage following reperfusion. In this study, we synthesize an antioxidant nanozyme, equipped with a single-Platinum (Pt)-atom (PtsaN-C), for protecting against I/R injury. PtsaN-C exhibits multiple enzyme-mimicking activities for ROS scavenging with high efficiency and stability. Mechanistic studies demonstrate that the excellent ROS-elimination performance of the single Pt atom center precedes that of the Pt cluster center, owing to its better synergistic effect and metallic electronic property. Systematic in vitro and in vivo studies confirm that PtsaN-C efficiently counteracts ROS, restores cellular homeostasis and prevents apoptotic progression after I/R injury. PtsaN-C also demonstrates good biocompatibility, making it a promising candidate for clinical applications. Our study expands the scope of single-atom nanozyme in combating ROS-induced damage and offers a promising therapeutic avenue for the treatment of I/R injury.
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Affiliation(s)
- Tianbao Ye
- Department of Cardiology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200233, Shanghai, China
- Institute for Personalized Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, 200030, Shanghai, China
| | - Cheng Chen
- Tongji Hospital, School of Medicine, Tongji University, 200092, Shanghai, China
| | - Di Wang
- Department of Cardiology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200233, Shanghai, China
- Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 200080, Shanghai, China
| | - Chengjie Huang
- Institute for Personalized Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, 200030, Shanghai, China
| | - Zhiwen Yan
- Youth Science and Technology Innovation Studio of Shanghai Jiao Tong University School of Medicine, 200233, Shanghai, China
| | - Yu Chen
- Department of Cardiology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200233, Shanghai, China
| | - Xian Jin
- Department of Cardiology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200233, Shanghai, China.
| | - Xiuyuan Wang
- Zhongshan Hospital, Fudan University, 200032, Shanghai, China.
| | - Xianting Ding
- Institute for Personalized Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, 200030, Shanghai, China.
| | - Chengxing Shen
- Department of Cardiology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200233, Shanghai, China.
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19
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Perera B, Wu Y, Nguyen NT, Ta HT. Advances in drug delivery to atherosclerosis: Investigating the efficiency of different nanomaterials employed for different type of drugs. Mater Today Bio 2023; 22:100767. [PMID: 37600355 PMCID: PMC10433009 DOI: 10.1016/j.mtbio.2023.100767] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Revised: 07/06/2023] [Accepted: 08/06/2023] [Indexed: 08/22/2023] Open
Abstract
Atherosclerosis is the build-up of fatty deposits in the arteries, which is the main underlying cause of cardiovascular diseases and the leading cause of global morbidity and mortality. Current pharmaceutical treatment options are unable to effectively treat the plaque in the later stages of the disease. Instead, they are aimed at resolving the risk factors. Nanomaterials and nanoparticle-mediated therapies have become increasingly popular for the treatment of atherosclerosis due to their targeted and controlled release of therapeutics. In this review, we discuss different types of therapeutics used to treat this disease and focus on the different nanomaterial strategies employed for the delivery of these drugs, enabling the effective and efficient resolution of the atherosclerotic plaque. The ideal nanomaterial strategy for each drug type (e.g. statins, nucleic acids, small molecule drugs, peptides) will be comprehensively discussed.
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Affiliation(s)
- Binura Perera
- School of Environment and Science, Griffith University, Nathan, Queensland, 4111, Australia
- Queensland Micro-Nanotechnology Centre, Griffith University, Nathan, Queensland, 4111, Australia
| | - Yuao Wu
- School of Environment and Science, Griffith University, Nathan, Queensland, 4111, Australia
| | - Nam-Trung Nguyen
- School of Environment and Science, Griffith University, Nathan, Queensland, 4111, Australia
| | - Hang Thu Ta
- School of Environment and Science, Griffith University, Nathan, Queensland, 4111, Australia
- Queensland Micro-Nanotechnology Centre, Griffith University, Nathan, Queensland, 4111, Australia
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20
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Zhang J, Guo Y, Bai Y, Wei Y. Application of biomedical materials in the diagnosis and treatment of myocardial infarction. J Nanobiotechnology 2023; 21:298. [PMID: 37626396 PMCID: PMC10463704 DOI: 10.1186/s12951-023-02063-2] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Accepted: 08/14/2023] [Indexed: 08/27/2023] Open
Abstract
Myocardial infarction (MI) is a cardiovascular emergency and the leading cause of death worldwide. Inflammatory and immune responses are initiated immediately after MI, leading to myocardial death, scarring, and ventricular remodeling. Current therapeutic approaches emphasize early restoration of ischemic myocardial reperfusion, but there is no effective treatment for the pathological changes of infarction. Biomedical materials development has brought new hope for MI diagnosis and treatment. Biomedical materials, such as cardiac patches, hydrogels, nano biomaterials, and artificial blood vessels, have played an irreplaceable role in MI diagnosis and treatment. They improve the accuracy and efficacy of MI diagnosis and offer further possibilities for reducing inflammation, immunomodulation, inhibiting fibrosis, and cardiac regeneration. This review focuses on the advances in biomedical materials applications in MI diagnosis and treatment. The current studies are outlined in terms of mechanisms of action and effects. It is addressed how biomedical materials application can lessen myocardial damage, encourage angiogenesis, and enhance heart function. Their clinical transformation value and application prospect are discussed.
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Affiliation(s)
- Jiahui Zhang
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Engineering Research Center for Immunological Diagnosis and Therapy of Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Yishan Guo
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Engineering Research Center for Immunological Diagnosis and Therapy of Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Department of Cardiology, Binzhou Medical University Hospital, Binzhou, 256600, China
| | - Yu Bai
- Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100000, China.
- National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, P.R. China.
| | - Yumiao Wei
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
- Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
- Hubei Engineering Research Center for Immunological Diagnosis and Therapy of Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
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21
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Soni SS, D'Elia AM, Rodell CB. Control of the post-infarct immune microenvironment through biotherapeutic and biomaterial-based approaches. Drug Deliv Transl Res 2023; 13:1983-2014. [PMID: 36763330 PMCID: PMC9913034 DOI: 10.1007/s13346-023-01290-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/03/2023] [Indexed: 02/11/2023]
Abstract
Ischemic heart failure (IHF) is a leading cause of morbidity and mortality worldwide, for which heart transplantation remains the only definitive treatment. IHF manifests from myocardial infarction (MI) that initiates tissue remodeling processes, mediated by mechanical changes in the tissue (loss of contractility, softening of the myocardium) that are interdependent with cellular mechanisms (cardiomyocyte death, inflammatory response). The early remodeling phase is characterized by robust inflammation that is necessary for tissue debridement and the initiation of repair processes. While later transition toward an immunoregenerative function is desirable, functional reorientation from an inflammatory to reparatory environment is often lacking, trapping the heart in a chronically inflamed state that perpetuates cardiomyocyte death, ventricular dilatation, excess fibrosis, and progressive IHF. Therapies can redirect the immune microenvironment, including biotherapeutic and biomaterial-based approaches. In this review, we outline these existing approaches, with a particular focus on the immunomodulatory effects of therapeutics (small molecule drugs, biomolecules, and cell or cell-derived products). Cardioprotective strategies, often focusing on immunosuppression, have shown promise in pre-clinical and clinical trials. However, immunoregenerative therapies are emerging that often benefit from exacerbating early inflammation. Biomaterials can be used to enhance these therapies as a result of their intrinsic immunomodulatory properties, parallel mechanisms of action (e.g., mechanical restraint), or by enabling cell or tissue-targeted delivery. We further discuss translatability and the continued progress of technologies and procedures that contribute to the bench-to-bedside development of these critically needed treatments.
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Affiliation(s)
- Shreya S Soni
- School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA, 19104, USA
| | - Arielle M D'Elia
- School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA, 19104, USA
| | - Christopher B Rodell
- School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA, 19104, USA.
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22
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Boswell-Patterson CA, Hétu MF, Pang SC, Herr JE, Zhou J, Jain S, Bambokian A, Johri AM. Novel theranostic approaches to neovascularized atherosclerotic plaques. Atherosclerosis 2023; 374:1-10. [PMID: 37149970 DOI: 10.1016/j.atherosclerosis.2023.04.008] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 04/05/2023] [Accepted: 04/17/2023] [Indexed: 05/09/2023]
Abstract
As the global burden of atherosclerotic cardiovascular disease continues to rise, there is an increased demand for improved imaging techniques for earlier detection of atherosclerotic plaques and new therapeutic targets. Plaque lesions, vulnerable to rupture and thrombosis, are thought to be responsible for the majority of cardiovascular events, and are characterized by a large lipid core, a thin fibrous cap, and neovascularization. In addition to supplying the plaque core with increased inflammatory factors, these pathological neovessels are tortuous and leaky, further increasing the risk of intraplaque hemorrhage. Clinically, plaque neovascularization has been shown to be a significant and independent predictor of adverse cardiovascular outcomes. Microvessels can be detected through contrast-enhanced ultrasound (CEUS) imaging, however, clinical assessment in vivo is generally limited to qualitative measures of plaque neovascularization. There is no validated standard for quantitative assessment of the microvessel networks found in plaques. Advances in our understanding of the pathological mechanisms underlying plaque neovascularization and its significant role in the morbidity and mortality associated with atherosclerosis have made it an attractive area of research in translational medicine. Current areas of research include the development of novel therapeutic and diagnostic agents to target plaque neovascularization stabilization. With recent progress in nanotechnology, nanoparticles have been investigated for their ability to specifically target neovascularization. Contrast microbubbles have been similarly engineered to carry loads of therapeutic agents and can be visualized using CEUS. This review summarizes the pathogenesis, diagnosis, clinical significance of neovascularization, and importantly the emerging areas of theranostic tool development.
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Affiliation(s)
| | - Marie-France Hétu
- Department of Medicine, Cardiovascular Imaging Network at Queen's (CINQ), Queen's University, Canada
| | - Stephen C Pang
- Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Canada
| | - Julia E Herr
- Department of Medicine, Cardiovascular Imaging Network at Queen's (CINQ), Queen's University, Canada
| | - Jianhua Zhou
- Department of Biomedical Engineering, Sun Yat-sen University, Guangzhou, China
| | - Shagun Jain
- Department of Medicine, Cardiovascular Imaging Network at Queen's (CINQ), Queen's University, Canada
| | - Alexander Bambokian
- Department of Medicine, Cardiovascular Imaging Network at Queen's (CINQ), Queen's University, Canada
| | - Amer M Johri
- Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Canada; Department of Medicine, Cardiovascular Imaging Network at Queen's (CINQ), Queen's University, Canada.
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23
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Jayakodi S, Senthilnathan R, Swaminathan A, Shanmugam VK, Shanmugam RK, Krishnan A, Ponnusamy VK, Tsai PC, Lin YC, Chen YH. Bio-inspired nanoparticles mediated from plant extract biomolecules and their therapeutic application in cardiovascular diseases: A review. Int J Biol Macromol 2023:125025. [PMID: 37245774 DOI: 10.1016/j.ijbiomac.2023.125025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 05/05/2023] [Accepted: 05/20/2023] [Indexed: 05/30/2023]
Abstract
Nanoparticles (NPs) have gained recognition for diagnosis, drug delivery, and therapy in fatal diseases. This review focuses on the benefits of green synthesis of bioinspired NPs using various plant extract (containing various biomolecules such as sugars, proteins, and other phytochemical compounds) and their therapeutic application in cardiovascular diseases (CVDs). Multiple factors including inflammation, mitochondrial and cardiomyocyte mutations, endothelial cell apoptosis, and administration of non-cardiac drugs, can trigger the cause of cardiac disorders. Furthermore, the interruption of reactive oxygen species (ROS) synchronization from mitochondria causes oxidative stress in the cardiac system, leading to chronic diseases such as atherosclerosis and myocardial infarction. NPs can decrease the interaction with biomolecules and prevent the incitement of ROS. Understanding this mechanism can pave the way for using green synthesized elemental NPs to reduce the risk of CVD. This review delivers information on the different methods, classifications, mechanisms and benefits of using NPs, as well as the formation and progression of CVDs and their effects on the body.
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Affiliation(s)
- Santhoshkumar Jayakodi
- Department of Biotechnology, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu 602105, India
| | - Raghul Senthilnathan
- Global Business School for Health, University College London, Gower St, London WC1E 6BT, United Kingdom
| | - Akila Swaminathan
- Clinical Virology, Manipal Institute of Virology, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India
| | - Venkat Kumar Shanmugam
- Department of Biotechnology, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu 632014, India
| | - Rajesh Kumar Shanmugam
- Department of Pharmacology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Science, Chennai, Tamil Nadu 600077, India
| | - Anbarasu Krishnan
- Department of Bioinformatics, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu 602105, India.
| | - Vinoth Kumar Ponnusamy
- Department of Medicinal and Applied Chemistry, Kaohsiung Medical University (KMU), Kaohsiung City 807, Taiwan; Research Center for Precision Environmental Medicine, Kaohsiung Medical University, Kaohsiung City 807, Taiwan; Department of Medical Research, Kaohsiung Medical University Hospital (KMUH), Kaohsiung City 807, Taiwan; Center for Emerging Contaminants Research, National Sun Yat-Sen University, Kaohsiung 804, Taiwan.
| | - Pei-Chien Tsai
- Department of Medicinal and Applied Chemistry, Kaohsiung Medical University (KMU), Kaohsiung City 807, Taiwan
| | - Yuan-Chung Lin
- Center for Emerging Contaminants Research, National Sun Yat-Sen University, Kaohsiung 804, Taiwan; Institute of Environmental Engineering, National Sun Yat-Sen University, Kaohsiung 804, Taiwan
| | - Yi-Hsun Chen
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung City, Taiwan.
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24
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Carvalho T, Bártolo R, Pedro SN, Valente BFA, Pinto RJB, Vilela C, Shahbazi MA, Santos HA, Freire CSR. Injectable Nanocomposite Hydrogels of Gelatin-Hyaluronic Acid Reinforced with Hybrid Lysozyme Nanofibrils-Gold Nanoparticles for the Regeneration of Damaged Myocardium. ACS APPLIED MATERIALS & INTERFACES 2023. [PMID: 37200222 DOI: 10.1021/acsami.3c03874] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/20/2023]
Abstract
Biopolymeric injectable hydrogels are promising biomaterials for myocardial regeneration applications. Besides being biocompatible, they adjust themselves, perfectly fitting the surrounding tissue. However, due to their nature, biopolymeric hydrogels usually lack desirable functionalities, such as antioxidant activity and electrical conductivity, and in some cases, mechanical performance. Protein nanofibrils (NFs), such as lysozyme nanofibrils (LNFs), are proteic nanostructures with excellent mechanical performance and antioxidant activity, which can work as nanotemplates to produce metallic nanoparticles. Here, gold nanoparticles (AuNPs) were synthesized in situ in the presence of LNFs, and the obtained hybrid AuNPs@LNFs were incorporated into gelatin-hyaluronic acid (HA) hydrogels for myocardial regeneration applications. The resulting nanocomposite hydrogels showed improved rheological properties, mechanical resilience, antioxidant activity, and electrical conductivity, especially for the hydrogels containing AuNPs@LNFs. The swelling and bioresorbability ratios of these hydrogels are favorably adjusted at lower pH levels, which correspond to the ones in inflamed tissues. These improvements were observed while maintaining important properties, namely, injectability, biocompatibility, and the ability to release a model drug. Additionally, the presence of AuNPs allowed the hydrogels to be monitorable through computer tomography. This work demonstrates that LNFs and AuNPs@LNFs are excellent functional nanostructures to formulate injectable biopolymeric nanocomposite hydrogels for myocardial regeneration applications.
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Affiliation(s)
- Tiago Carvalho
- CICECO - Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, Campus de Santiago, 3810-193 Aveiro, Portugal
- Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland
| | - Raquel Bártolo
- Department of Biomedical Engineering, University Medical Center Groningen, University of Groningen, Ant. Deusinglaan 1, 9713 AV Groningen, The Netherlands
- W.J. Kolff Institute for Biomedical Engineering and Materials Science, University Medical Center Groningen, University of Groningen, Ant. Deusinglaan 1, 9713 AV Groningen, The Netherlands
| | - Sónia N Pedro
- CICECO - Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, Campus de Santiago, 3810-193 Aveiro, Portugal
| | - Bruno F A Valente
- CICECO - Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, Campus de Santiago, 3810-193 Aveiro, Portugal
| | - Ricardo J B Pinto
- CICECO - Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, Campus de Santiago, 3810-193 Aveiro, Portugal
| | - Carla Vilela
- CICECO - Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, Campus de Santiago, 3810-193 Aveiro, Portugal
| | - Mohammad-Ali Shahbazi
- Department of Biomedical Engineering, University Medical Center Groningen, University of Groningen, Ant. Deusinglaan 1, 9713 AV Groningen, The Netherlands
- W.J. Kolff Institute for Biomedical Engineering and Materials Science, University Medical Center Groningen, University of Groningen, Ant. Deusinglaan 1, 9713 AV Groningen, The Netherlands
| | - Hélder A Santos
- Department of Biomedical Engineering, University Medical Center Groningen, University of Groningen, Ant. Deusinglaan 1, 9713 AV Groningen, The Netherlands
- W.J. Kolff Institute for Biomedical Engineering and Materials Science, University Medical Center Groningen, University of Groningen, Ant. Deusinglaan 1, 9713 AV Groningen, The Netherlands
- Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland
| | - Carmen S R Freire
- CICECO - Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, Campus de Santiago, 3810-193 Aveiro, Portugal
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25
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Leong MY, Kong YL, Burgess K, Wong WF, Sethi G, Looi CY. Recent Development of Nanomaterials for Transdermal Drug Delivery. Biomedicines 2023; 11:biomedicines11041124. [PMID: 37189742 DOI: 10.3390/biomedicines11041124] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 03/21/2023] [Accepted: 03/24/2023] [Indexed: 05/17/2023] Open
Abstract
Nano-engineered medical products first appeared in the last decade. The current research in this area focuses on developing safe drugs with minimal adverse effects associated with the pharmacologically active cargo. Transdermal drug delivery, an alternative to oral administration, offers patient convenience, avoids first-pass hepatic metabolism, provides local targeting, and reduces effective drug toxicities. Nanomaterials provide alternatives to conventional transdermal drug delivery including patches, gels, sprays, and lotions, but it is crucial to understand the transport mechanisms involved. This article reviews the recent research trends in transdermal drug delivery and emphasizes the mechanisms and nano-formulations currently in vogue.
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Affiliation(s)
- Moong Yan Leong
- School of Biosciences, Faculty of Health and Medical Sciences, Taylor's University Lakeside Campus, Subang Jaya, Selangor Darul Ehsan 47500, Malaysia
| | - Yeo Lee Kong
- Department of Engineering and Applied Science, America Degree Program, Taylor's University Lakeside Campus, Subang Jaya, Selangor Darul Ehsan 47500, Malaysia
| | - Kevin Burgess
- Department of Chemistry, Texas A&M University, P.O. Box 30012, College Station, TX 77842, USA
| | - Won Fen Wong
- Department of Medical Microbiology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, Malaysia
| | - Gautam Sethi
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore
| | - Chung Yeng Looi
- School of Biosciences, Faculty of Health and Medical Sciences, Taylor's University Lakeside Campus, Subang Jaya, Selangor Darul Ehsan 47500, Malaysia
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26
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Wang Q, Wang T, Lio C, Yu X, Chen X, Liu L, Wu Y, Huang H, Qing L, Luo P. Surface hydrolysis-designed AuNPs-zwitterionic-glucose as a novel tool for targeting macrophage visualization and delivery into infarcted hearts. J Control Release 2023; 356:678-690. [PMID: 36898530 DOI: 10.1016/j.jconrel.2023.03.008] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Revised: 02/27/2023] [Accepted: 03/05/2023] [Indexed: 03/12/2023]
Abstract
Macrophages, innate immune cells, are key players in the maintenance of myocardial homeostasis under normal conditions and tissue repair after injury. The infiltration of macrophages into the injured heart makes them a potentially appealing vehicle for noninvasive imaging and targeted drug delivery of myocardial infarction (MI). In this study, we demonstrated the use of surface hydrolysis-designed AuNPs-zwitterionic-glucose to label macrophages and track their infiltration into isoproterenol hydrochloride (ISO)-induced MI sites noninvasively using CT. The AuNPs-zwitterionic-glucose did not affect the viability or cytokine release of macrophages and were highly taken up by these cells. The in vivo CT images were obtained on Day 4, Day 6, Day 7, and Day 9, and the attenuation was seen to increase in the heart over time compared to the Day 4 scan. In vitro analysis also confirmed the presence of macrophages around injured cardiomyocytes. Additionally, we also addressed the concern of cell tracking or merely AuNP tracking, which is the inherent problem for any form of nanoparticle-labeled cell tracking by using zwitterionic and glucose-functionalized AuNPs. The glucose coated on the surface of AuNPs-zwit-glucose will be hydrolyzed in macrophages, forming only zwitterionic protected AuNPs that cannot be taken up again by endogenous cells in vivo. This will greatly improve the accuracy and precision of imaging and target delivery. We believe this is the first study to noninvasively visualize the infiltration of macrophages into MI hearts using CT, which could be used for imaging and evaluating the possibility of macrophage-mediated delivery in infarcted hearts.
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Affiliation(s)
- Qianlong Wang
- State Key Laboratories for Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau 999078, China; Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China; School of Materials Science and Engineering, Tsinghua University, Beijing 100084, China
| | - Tiantian Wang
- State Key Laboratories for Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau 999078, China; Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China
| | - Chonkit Lio
- State Key Laboratories for Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau 999078, China
| | - Xina Yu
- State Key Laboratories for Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau 999078, China
| | - Xiaoyi Chen
- State Key Laboratories for Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau 999078, China
| | - Lancong Liu
- State Key Laboratories for Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau 999078, China
| | - Youjiao Wu
- State Key Laboratories for Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau 999078, China
| | - Hui Huang
- Department of Cardiology, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518000, China
| | - Linsen Qing
- Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China.
| | - Pei Luo
- State Key Laboratories for Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau 999078, China.
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27
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Zhang X, Centurion F, Misra A, Patel S, Gu Z. Molecularly targeted nanomedicine enabled by inorganic nanoparticles for atherosclerosis diagnosis and treatment. Adv Drug Deliv Rev 2023; 194:114709. [PMID: 36690300 DOI: 10.1016/j.addr.2023.114709] [Citation(s) in RCA: 31] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 12/20/2022] [Accepted: 01/17/2023] [Indexed: 01/22/2023]
Abstract
Atherosclerosis, a chronic cardiovascular disease caused by plaque development in arteries, remains a leading cause of morbidity and mortality. Atherosclerotic plaques are characterized by the expression and regulation of key molecules such as cell surface receptors, cytokines, and signaling pathway proteins, potentially facilitating precise diagnosis and treatment on a molecular level by specifically targeting the characteristic molecules. In this review, we highlight the recent progress in the past five years on developing molecularly targeted nanomedicine for imaging detection and treatment of atherosclerosis with the use of inorganic nanoparticles. Through targeted delivery of imaging contrast nanoparticles to specific molecules in atherogenesis, atherosclerotic plaque development at different stages could be identified and monitored via various molecular imaging modalities. We also review molecularly targeted therapeutic approaches that target and regulate molecules associated with lipid regulation, inflammation, and apoptosis. The review is concluded with discussion on current challenges and future development of nanomedicine for atherosclerotic diagnosis and treatment.
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Affiliation(s)
- Xiuwen Zhang
- School of Chemical Engineering, University of New South Wales, Sydney, NSW 2052, Australia
| | - Franco Centurion
- School of Chemical Engineering, University of New South Wales, Sydney, NSW 2052, Australia
| | - Ashish Misra
- Heart Research Institute, Sydney, NSW 2042, Australia; Faculty of Medicine and Health, The University of Sydney, NSW 2006, Australia
| | - Sanjay Patel
- Heart Research Institute, Sydney, NSW 2042, Australia; Royal Prince Alfred Hospital, Sydney, NSW 2050, Australia; Sydney Medical School, The University of Sydney, NSW 2006, Australia
| | - Zi Gu
- School of Chemical Engineering, University of New South Wales, Sydney, NSW 2052, Australia; Australian Centre for NanoMedicine (ACN), University of New South Wales, Sydney, NSW 2052, Australia; UNSW RNA Institute, University of New South Wales, Sydney, NSW 2052, Australia.
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28
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Chen X, Dai C, Hu R, Yu L, Chen Y, Zhang B. Engineering ROS-scavenging Prussian blue nanozymes for efficient atherosclerosis nanotherapy. J Mater Chem B 2023; 11:1881-1890. [PMID: 36723250 DOI: 10.1039/d2tb02661a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Atherosclerosis (AS), characterized by a chronic inflammatory disease, is a top cause of morbidity and disability worldwide. During the pathogenesis of AS, the leading process of inflammation highly involves a secondary event of oxidative stress, but limited antioxidants are currently available clinically due to their nonspecific effects, poor biosafety, and rapid in vivo elimination and urinary excretion as well as short retention time within plaque lesions. In this work, Prussian blue nanozymes with a strong reactive oxygen species (ROS)-scavenging ability were rationally engineered for efficient AS nanotherapy. Specifically, the obtained nanozymes with high photothermal performance could behave as potent photoacoustic imaging agents for plaque detection. In addition, these nanozymes featuring multienzyme activities could reduce the cellular ROS level, exert cytoprotective effects against ROS-mediated macrophages apoptosis, and inhibit foam cell formation, significantly boycotting AS development. The underlying mechanism was further verified by transcriptome sequencing at the cellular level and a series of immunohistochemical staining of aortic sinus sections in apoE-/- mice. Finally, the high biocompatibility and biosafety of the engineered Prussian blue nanozymes further guarantee their clinical translation potential for AS management.
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Affiliation(s)
- Xiaoying Chen
- Department of Ultrasound, Shanghai East Hospital, Tongji University, Shanghai 200120, P. R. China.
| | - Chen Dai
- Department of Ultrasound, Shanghai East Hospital, Tongji University, Shanghai 200120, P. R. China.
| | - Ruizhi Hu
- Department of Ultrasound, Shanghai East Hospital, Tongji University, Shanghai 200120, P. R. China.
| | - Luodan Yu
- Materdicine Lab, School of Life Sciences, Shanghai University, Shanghai 200444, P. R. China.
| | - Yu Chen
- Materdicine Lab, School of Life Sciences, Shanghai University, Shanghai 200444, P. R. China.
| | - Bo Zhang
- Department of Ultrasound, Shanghai East Hospital, Tongji University, Shanghai 200120, P. R. China.
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29
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Gong Y, Liu H, Ke S, Zhuo L, Wang H. Latest advances in biomimetic nanomaterials for diagnosis and treatment of cardiovascular disease. Front Cardiovasc Med 2023; 9:1037741. [PMID: 36684578 PMCID: PMC9846151 DOI: 10.3389/fcvm.2022.1037741] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Accepted: 12/09/2022] [Indexed: 01/05/2023] Open
Abstract
Cardiovascular disease remains one of the leading causes of death in China, with increasingly serious negative effects on people and society. Despite significant advances in preventing and treating cardiovascular diseases, such as atrial fibrillation/flutter and heart failure over the last few years, much more remains to be done. Therefore, developing innovative methods for identifying and managing cardiovascular disorders is critical. Nanomaterials provide multiple benefits in biomedicine, primarily better catalytic activity, drug loading, targeting, and imaging. Biomimetic materials and nanoparticles are specially combined to synthesize biomimetic nanoparticles that successfully reduce the nanoparticles' toxicity and immunogenicity while enhancing histocompatibility. Additionally, the biological targeting capability of nanoparticles facilitates the diagnosis and therapy of cardiovascular disease. Nowadays, nanomedicine still faces numerous challenges, which necessitates creating nanoparticles that are highly selective, toxic-free, and better clinically applicable. This study reviews the scientific accomplishments in this field over the past few years covering the classification, applications, and prospects of noble metal biomimetic nanozymes and biomimetic nanocarriers.
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Affiliation(s)
- Yuxuan Gong
- College of Life Sciences and Bioengineering, School of Physical Science and Engineering, Beijing Jiaotong University, Beijing, China
| | - Huaying Liu
- College of Life Sciences and Bioengineering, School of Physical Science and Engineering, Beijing Jiaotong University, Beijing, China
| | - Shen Ke
- College of Life Sciences and Bioengineering, School of Physical Science and Engineering, Beijing Jiaotong University, Beijing, China
| | - Li Zhuo
- Department of Nephrology, China-Japan Friendship Hospital, Beijing, China,Li Zhuo,
| | - Haibin Wang
- College of Life Sciences and Bioengineering, School of Physical Science and Engineering, Beijing Jiaotong University, Beijing, China,*Correspondence: Haibin Wang,
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30
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Shi T, Miller EJ. Novel Radiotracers for Molecular Imaging of Myocardial Inflammation: an Update Focused on Clinical Translation of Non-18F-FDG Radiotracers. CURRENT CARDIOVASCULAR IMAGING REPORTS 2023; 16:1-9. [PMID: 36926261 PMCID: PMC9996562 DOI: 10.1007/s12410-023-09574-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/26/2023] [Indexed: 03/11/2023]
Abstract
Purpose of Review The purpose of this paper is to provide a focused update on recent advances in non-18F-FDG radiotracers for myocardial inflammatory diseases, with a focus on cardiac sarcoidosis and myocarditis. Recent Findings Novel radiotracers targeting molecular features of inflammation have the potential to visualize underlying molecular mechanisms key to the pathogenesis of inflammatory cardiomyopathies such as sarcoidosis and myocarditis. These radiotracers may provide unique opportunities for improved mechanistic insight, higher specificity, and better quantification of disease activity, as well as potential for guidance and monitoring of immunomodulatory therapies. Summary Novel radiotracers provide unique possibilities in diagnosis, prognostic performance, and therapy guidance for cardiac sarcoidosis and myocarditis.
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Affiliation(s)
- Tiantian Shi
- Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, CT USA
| | - Edward J Miller
- Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, CT USA
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31
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Tu Y, Ma X, Chen H, Fan Y, Jiang L, Zhang R, Cheng Z. Molecular Imaging of Matrix Metalloproteinase-2 in Atherosclerosis Using a Smart Multifunctional PET/MRI Nanoparticle. Int J Nanomedicine 2022; 17:6773-6789. [PMID: 36600879 PMCID: PMC9805955 DOI: 10.2147/ijn.s385679] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Accepted: 11/09/2022] [Indexed: 12/29/2022] Open
Abstract
Background Matrix metalloproteinases from macrophages are important intraplaque components that play pivotal roles in plaque progression and regression. This study sought to develop a novel multifunctional positron emission tomography (PET) and magnetic resonance imaging (MRI) contrast agents based on MMP-2 cleavable nanoparticles to noninvasive assessment of MMP-2 activity in mouse carotid atherosclerotic plaques. Results Macrophage-rich vascular lesions were induced by carotid ligation plus high-fat diet and streptozotocin-induced diabetes in CL57/BL6 mice. To render iron oxide nanoparticles (IONP) specific for the extracellular MMP-2, the magnetic nanoparticle base material has been derivatized with 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) for the nuclear tracer 64Cu labeling and the MMP-2-cleavable peptide modified with polyethylene glycol 2000, yielding a multi-modality reporter (64Cu-NOTA-IONP@MMP2c-PEG2K, MMP2cNPs) for PET/MR imaging. Small animal PET imaging and biodistribution data revealed that MMP2cNPs exhibited remarkable plaque uptake (3.06 ± 0.87% ID/g and 1.83 ± 0.28% ID/g at 4 and 12 h, respectively). And MMP2cNPs were rapidly cleared from the contralateral normal carotid artery, resulting in excellent plaque-to-normal carotid artery contrasts. Furthermore, in vivo MRI showed a preferential accumulation of MMP2cNPs in atherosclerotic lesions compared with the non-cleavable reference compound, MMP2ncNPs. In addition, histological analyses revealed iron accumulations in the carotid atherosclerotic plaque, in colocalization with MMP-2 expression and macrophages. Conclusion Using a combination of innovative imaging modalities, in this study, we demonstrate the feasibility of applying the novel smart MMP2cNPs as a PET/MR hybrid imaging contrast agent for detection of MMP-2 in atherosclerotic plaque in vivo.
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Affiliation(s)
- Yingfeng Tu
- Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China,Molecular Imaging Program at Stanford, Department of Radiology and Bio-X Program, Stanford University, Stanford, CA, USA
| | - Xiaowei Ma
- Department of Nuclear Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China
| | - Hao Chen
- Molecular Imaging Program at Stanford, Department of Radiology and Bio-X Program, Stanford University, Stanford, CA, USA,Molecular Imaging Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People’s Republic of China
| | - Yuhua Fan
- College of Pharmacy, Harbin Medical University, Daqing, Heilongjiang, People’s Republic of China
| | - Lei Jiang
- Molecular Imaging Program at Stanford, Department of Radiology and Bio-X Program, Stanford University, Stanford, CA, USA
| | - Ruiping Zhang
- Molecular Imaging Program at Stanford, Department of Radiology and Bio-X Program, Stanford University, Stanford, CA, USA,The Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Taiyuan, People’s Republic of China,Ruiping Zhang, Department of Radiology, the Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Taiyuan, 030032, People’s Republic of China, Email
| | - Zhen Cheng
- Molecular Imaging Program at Stanford, Department of Radiology and Bio-X Program, Stanford University, Stanford, CA, USA,Molecular Imaging Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People’s Republic of China,Correspondence: Zhen Cheng, Molecular Imaging Program at Stanford, Department of Radiology and Bio-X Program, Canary Center at Stanford for Cancer Early Detection, 1201 Welch Road, Lucas Expansion, P095, Stanford University, Stanford, CA, 94305, USA, Tel +01-650-723-7866, Email
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32
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Muthwill MS, Kong P, Dinu IA, Necula D, John C, Palivan CG. Tailoring Polymer-Based Nanoassemblies for Stimuli-Responsive Theranostic Applications. Macromol Biosci 2022; 22:e2200270. [PMID: 36100461 DOI: 10.1002/mabi.202200270] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Revised: 08/28/2022] [Indexed: 12/25/2022]
Abstract
Polymer assemblies on the nanoscale represent a powerful toolbox for the design of theranostic systems when combined with both therapeutic compounds and diagnostic reporting ones. Here, recent advances in the design of theranostic systems for various diseases, containing-in their architecture-either polymers or polymer assemblies as one of the building blocks are presented. This review encompasses the general principles of polymer self-assembly, from the production of adequate copolymers up to supramolecular assemblies with theranostic functionality. Such polymer nanoassemblies can be further tailored through the incorporation of inorganic nanoparticles to endow them with multifunctional therapeutic and/or diagnostic features. Systems that change their architecture or properties in the presence of stimuli are selected, as responsivity to changes in the environment is a key factor for enhancing efficiency. Such theranostic systems are based on the intrinsic properties of copolymers or one of the other components. In addition, systems with a more complex architecture, such as multicompartments, are presented. Selected systems indicate the advantages of such theranostic approaches and provide a basis for further developments in the field.
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Affiliation(s)
- Moritz S Muthwill
- Department of Chemistry, University of Basel, Mattenstrasse 24a, BPR 1096, Basel, 4058, Switzerland.,NCCR-Molecular Systems Engineering, Mattenstrasse 24a, BPR 1095, Basel, 4058, Switzerland
| | - Phally Kong
- Department of Chemistry, University of Basel, Mattenstrasse 24a, BPR 1096, Basel, 4058, Switzerland
| | - Ionel Adrian Dinu
- Department of Chemistry, University of Basel, Mattenstrasse 24a, BPR 1096, Basel, 4058, Switzerland
| | - Danut Necula
- Department of Chemistry, University of Basel, Mattenstrasse 24a, BPR 1096, Basel, 4058, Switzerland
| | - Christoph John
- Department of Chemistry, University of Basel, Mattenstrasse 24a, BPR 1096, Basel, 4058, Switzerland
| | - Cornelia G Palivan
- Department of Chemistry, University of Basel, Mattenstrasse 24a, BPR 1096, Basel, 4058, Switzerland.,NCCR-Molecular Systems Engineering, Mattenstrasse 24a, BPR 1095, Basel, 4058, Switzerland
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Hu R, Dai C, Dong C, Ding L, Huang H, Chen Y, Zhang B. Living Macrophage-Delivered Tetrapod PdH Nanoenzyme for Targeted Atherosclerosis Management by ROS Scavenging, Hydrogen Anti-inflammation, and Autophagy Activation. ACS NANO 2022; 16:15959-15976. [PMID: 36219731 DOI: 10.1021/acsnano.2c03422] [Citation(s) in RCA: 76] [Impact Index Per Article: 25.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
Atherosclerosis, driven by chronic inflammation in the artery walls, underlies several severe cardiovascular diseases. However, currently available anti-inflammatory-based strategies for atherosclerosis treatment suffer from compromised therapeutic efficacy and undesirable therapeutic outcome. Herein, a distinct tetrapod needle-like PdH nanozyme was designed and engineered for efficient atherosclerosis treatment by the combinatorial reactive oxygen species (ROS) scavenging, hydrogen anti-inflammation, and autophagy activation. After loading into macrophages and targeted delivery to arterial plaques, these multifunctional nanozymes efficiently decreased the ROS levels and significantly suppressed the inflammation-related pathological process, exerting the distinct antioxidation and anti-inflammatory performance for alleviating atherosclerosis development. Especially and importantly, the specific spiky morphology of the PdH nanoenzyme further triggered a strong autophagy response in macrophages, synergistically maintaining the cellular homeostasis and alleviating atherosclerosis development. Both in vitro and in vivo results confirmed the synergy among the antioxidation, anti-inflammatory, and autophagy activation, suggesting that the combinatorial engineering of nanomedicines with intrinsic multiple therapeutic functions and topology-induced biological effects is highly preferable and effective for achieving the high therapeutic performance and desirable therapeutic outcome on atherosclerosis management and therapy.
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Affiliation(s)
- Ruizhi Hu
- Department of Medical Ultrasound, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, P. R. China
| | - Chen Dai
- Department of Medical Ultrasound, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, P. R. China
| | - Caihong Dong
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032, P. R. China
| | - Li Ding
- Department of Medical Ultrasound, Shanghai Tenth People's Hospital, Ultrasound Research and Education Institute, Shanghai Engineering Research Center of Ultrasound Diagnosis and Treatment, Tongji University Cancer Center, School of Medicine, Tongji University, Shanghai 200072, P. R. China
| | - Hui Huang
- Materdicine Lab, School of Life Sciences, Shanghai University, Shanghai 200444, P. R. China
| | - Yu Chen
- Materdicine Lab, School of Life Sciences, Shanghai University, Shanghai 200444, P. R. China
| | - Bo Zhang
- Department of Medical Ultrasound, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, P. R. China
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Chen X, Ma Y, Xie Y, Pu J. Aptamer-based applications for cardiovascular disease. Front Bioeng Biotechnol 2022; 10:1002285. [PMID: 36312558 PMCID: PMC9606242 DOI: 10.3389/fbioe.2022.1002285] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Accepted: 09/20/2022] [Indexed: 11/13/2022] Open
Abstract
Cardiovascular disease (especially atherosclerosis) is a major cause of death worldwide, and novel diagnostic tools and treatments for this disease are urgently needed. Aptamers are single-stranded oligonucleotides that specifically recognize and bind to the targets by forming unique structures in vivo, enabling them to rival antibodies in cardiac applications. Chemically synthesized aptamers can be readily modified in a site-specific way, so they have been engineered in the diagnosis of cardiac diseases and anti-thrombosis therapeutics. Von Willebrand Factor plays a unique role in the formation of thrombus, and as an aptamer targeting molecule, has shown initial success in antithrombotic treatment. A combination of von Willebrand Factor and nucleic acid aptamers can effectively inhibit the progression of blood clots, presenting a positive diagnosis and therapeutic effect, as well as laying a novel theory and strategy to improve biocompatibility paclitaxel drug balloon or implanted stent in the future. This review summarizes aptamer-based applications in cardiovascular disease, including biomarker discovery and future management strategy. Although relevant applications are relatively new, the significant advancements achieved have demonstrated that aptamers can be promising agents to realize the integration of diagnosis and therapy in cardiac research.
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Affiliation(s)
| | | | | | - Jun Pu
- *Correspondence: Yuquan Xie, ; Jun Pu,
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Synthesis and Characterization of Fucoidan-Chitosan Nanoparticles Targeting P-Selectin for Effective Atherosclerosis Therapy. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:8006642. [PMID: 36120595 PMCID: PMC9481351 DOI: 10.1155/2022/8006642] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/28/2022] [Accepted: 08/22/2022] [Indexed: 11/18/2022]
Abstract
Atherosclerosis is the key pathogenesis of cardiovascular diseases; oxidative stress, which is induced by the generated excess reactive oxygen species (ROS), has been a crucial mechanism underlying this pathology. Nanoparticles (NPs) represent a novel strategy for the development of potential therapies against atherosclerosis, and multifunctional NPs possessing antioxidative capacities hold promise for amelioration of vascular injury caused by ROS and for evading off-target effects; materials that are currently used for NP synthesis often serve as vehicles that do not possess intrinsic biological activities; however, they may affect the surrounding healthy environment due to decomposition of products. Herein, we used nontoxic fucoidan, a sulfated polysaccharide derived from a marine organism, to develop chitosan–fucoidan nanoparticles (CFNs). Then, by binding to P-selectin, an inflammatory adhesion exhibited molecule expression on the endothelial cells and activated platelets, blocking leukocyte recruitment and rolling on platelets and endothelium. CFNs exhibit antioxidant and anti-inflammatory properties. Nevertheless, by now, the application of CFNs for the target delivery regarding therapeutics specific to atherosclerotic plaques is not well investigated. The produced CFNs were physicochemically characterized using transmission electron microscopy (TEM), together with Fourier transform infrared spectroscopy (FTIR). Evaluations of the in vitro antioxidant as well as anti-inflammatory activities exhibited by CFNs were based on the measurement of their ROS scavenging abilities and investigating inflammatory mediator levels. The in vivo pharmacokinetics and binding efficiency of the CFNs to atherosclerotic plaques were also evaluated. The therapeutic effects indicated that CFNs effectively suppressed local oxidative stress and inflammation by targeting P-selectin in atheromatous plaques and thereby preventing the progression of atherosclerosis.
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Obaid EAMS, Wu S, Zhong Y, Yan M, Zhu L, Li B, Wang Y, Wu W, Wang G. pH-Responsive hyaluronic acid-enveloped ZIF-8 nanoparticles for anti-atherosclerosis therapy. Biomater Sci 2022; 10:4837-4847. [PMID: 35858474 DOI: 10.1039/d2bm00603k] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Nanomedicines represent new promising strategies for treating atherosclerosis (AS), because they enhance drug bioavailability and have lower side effects. Nevertheless, nanomedicines have several challenges with these advantages, including a limited circulation life, lack of precise targeting, and insufficient control of drug release. Accordingly, the development of drug delivery systems (DDSs) with abilities to enhance the payload delivery to the AS plaque lesion and to control drug release can boost the therapeutic efficacy and safety for AS treatment. Herein, we employed a one-step self-assembly approach for effectively encapsulating the anti-AS drug simvastatin (SIM) in zeolitic imidazolate framework-8 (ZIF-8) (SIM/ZIF-8), and then coated it with hyaluronic acid (HA) to fabricate the SIM/ZIF-8@HA nanoplatform. The resulting nanoplatform could efficiently accumulate in plaque regions through the specific recognition between HA and CD44. Meanwhile, the acid environment breaks down ZIF-8 to release SIM. The in vitro and in vivo experiments demonstrated that SIM/ZIF-8@HA could inhibit the proliferation of smooth muscle cells and have good biocompatibility. Moreover, SIM/ZIF-8@HA can effectively suppress the development of AS plaques without any considerable side effects in mice treatments. The findings revealed that SIM/ZIF-8@HA may be a promising nanomedicine for safe and efficient anti-AS applications.
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Affiliation(s)
- Essam Abdo Mohammed Saad Obaid
- Key Laboratory of Biorheological and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Modern Life Science Experiment Teaching Center at Bioengineering College of Chongqing University, Chongqing 400030, China.
| | - Shuai Wu
- Key Laboratory of Biorheological and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Modern Life Science Experiment Teaching Center at Bioengineering College of Chongqing University, Chongqing 400030, China.
| | - Yuan Zhong
- Key Laboratory of Biorheological and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Modern Life Science Experiment Teaching Center at Bioengineering College of Chongqing University, Chongqing 400030, China.
| | - Meng Yan
- Key Laboratory of Biorheological and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Modern Life Science Experiment Teaching Center at Bioengineering College of Chongqing University, Chongqing 400030, China.
| | - Li Zhu
- Key Laboratory of Biorheological and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Modern Life Science Experiment Teaching Center at Bioengineering College of Chongqing University, Chongqing 400030, China.
| | - Bibo Li
- Department of Oncology, Chongqing People's Hospital, Chongqing 401147, China
| | - Yi Wang
- Key Laboratory of Biorheological and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Modern Life Science Experiment Teaching Center at Bioengineering College of Chongqing University, Chongqing 400030, China. .,College of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China
| | - Wei Wu
- Key Laboratory of Biorheological and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Modern Life Science Experiment Teaching Center at Bioengineering College of Chongqing University, Chongqing 400030, China.
| | - Guixue Wang
- Key Laboratory of Biorheological and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Modern Life Science Experiment Teaching Center at Bioengineering College of Chongqing University, Chongqing 400030, China.
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Xu H, Li S, Liu YS. Nanoparticles in the diagnosis and treatment of vascular aging and related diseases. Signal Transduct Target Ther 2022; 7:231. [PMID: 35817770 PMCID: PMC9272665 DOI: 10.1038/s41392-022-01082-z] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Revised: 06/23/2022] [Accepted: 06/26/2022] [Indexed: 11/09/2022] Open
Abstract
Aging-induced alternations of vasculature structures, phenotypes, and functions are key in the occurrence and development of vascular aging-related diseases. Multiple molecular and cellular events, such as oxidative stress, mitochondrial dysfunction, vascular inflammation, cellular senescence, and epigenetic alterations are highly associated with vascular aging physiopathology. Advances in nanoparticles and nanotechnology, which can realize sensitive diagnostic modalities, efficient medical treatment, and better prognosis as well as less adverse effects on non-target tissues, provide an amazing window in the field of vascular aging and related diseases. Throughout this review, we presented current knowledge on classification of nanoparticles and the relationship between vascular aging and related diseases. Importantly, we comprehensively summarized the potential of nanoparticles-based diagnostic and therapeutic techniques in vascular aging and related diseases, including cardiovascular diseases, cerebrovascular diseases, as well as chronic kidney diseases, and discussed the advantages and limitations of their clinical applications.
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Affiliation(s)
- Hui Xu
- Department of Geriatrics, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China.,Institute of Aging and Age-related Disease Research, Central South University, 410011, Changsha, Hunan, China
| | - Shuang Li
- Department of Geriatrics, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China.,Institute of Aging and Age-related Disease Research, Central South University, 410011, Changsha, Hunan, China
| | - You-Shuo Liu
- Department of Geriatrics, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China. .,Institute of Aging and Age-related Disease Research, Central South University, 410011, Changsha, Hunan, China.
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Sun Y, Liu M, Xiao Y, Chen Y. A novel molecular communication inspired detection method for the evolution of atherosclerosis. COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE 2022; 219:106756. [PMID: 35320741 DOI: 10.1016/j.cmpb.2022.106756] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 03/08/2022] [Accepted: 03/11/2022] [Indexed: 06/14/2023]
Abstract
BACKGROUND AND OBJECTIVE Atherosclerosis is a leading cause of potentially serious cardiovascular diseases such as heart attack, stroke, and peripheral artery disease. Due to the prolonged and non-reversible process of thickening arteries walls, atherosclerosis plaques in the blood vessels are formed that restrict the blood flow. Early detection plays a vital role in minimizing the risk as there is no reliable method to detect the early stage of the disease. This paper proposes a novel atherosclerosis detection method based on the emerging paradigm of molecular communications. The work could pave the way to implement a low-cost and straightforward early detection method of atherosclerosis in the future. METHODS We used COMSOL to model the physical field, coupled the fluid module and the fluid particle tracking module, and mapped the contrast agent into nanoparticles (NPs). The NPs are released at the entrance of the blood vessel and received at the exit of the blood vessel, while NPs are propagating through different arterial stenosis. The arrival probability of NPs is defined as the ratio of the number of NPs that reach the outlet to the total number of released NPs. As a result of atherosclerosis, the arrival probability of Nps is affected by the dynamic flow nature changes, thereby reflecting the arterial stenosis degree. Furthermore, we introduce the multi-release method in this study, which has a similar concept of Inter-symbol interference in traditional communication. This multi-release method leads the overlapping concentrations of NPs remaining in the vessels and enhances the differences of arrival probability in different degrees of stenosis, which increases the chance of more observable results. RESULTS The assessment of arterial stenosis degree can be from the early stage to the late stage of the disease. To evaluate the arterial stenosis degree, we analyzed the Poincaré maps, representing the arrival probability of NPs at different arterial stenosis. Moreover, we could directly use data to quantify the pathological process at various stages. The difference between the data results obtained through multiple release methods is more prominent than a single-released method. CONCLUSIONS This research proposes a new atherosclerosis detection method based on molecular communication, that is, to evaluate the arterial stenosis degree by modelling and using statistical data of NPs emission and reception in blood vessels. This method can not only use a simple method to detect the early stage of the disease. In addition, we can directly use data to quantify the pathological process of each stage, which is straightforward to assist doctors and may reduce the labour cost of traditional detection.
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Affiliation(s)
- Yue Sun
- School of Mechanical and Electrical Engineering, Chengdu University of Technology, Chengdu 610059, China; School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 611731, China
| | - Meiling Liu
- School of Mechanical and Electrical Engineering, Chengdu University of Technology, Chengdu 610059, China
| | - Yue Xiao
- School of Mechanical and Electrical Engineering, Chengdu University of Technology, Chengdu 610059, China
| | - Yifan Chen
- Yangtze Delta Region Institute (Huzhou), University of Electronic Science and Technology of China, Huzhou, China; School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 611731, China.
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Ramirez-Carracedo R, Sanmartin M, Ten A, Hernandez I, Tesoro L, Diez-Mata J, Botana L, Ovejero-Paredes K, Filice M, Alberich-Bayarri A, Martí-Bonmatí L, Largo-Aramburu C, Saura M, Zamorano JL, Zaragoza C. Theranostic Contribution of Extracellular Matrix Metalloprotease Inducer-Paramagnetic Nanoparticles Against Acute Myocardial Infarction in a Pig Model of Coronary Ischemia-Reperfusion. Circ Cardiovasc Imaging 2022; 15:e013379. [PMID: 35678191 PMCID: PMC9213084 DOI: 10.1161/circimaging.121.013379] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Rapid screening and accurate diagnosis of acute myocardial infarction are critical to reduce the progression of myocardial necrosis, in which proteolytic degradation of myocardial extracellular matrix plays a major role. In previous studies, we found that targeting the extracellular matrix metalloprotease inducer (EMMPRIN) by injecting nanoparticles conjugated with the specific EMMPRIN-binding peptide AP9 significantly improved cardiac function in mice subjected to ischemia/reperfusion.
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Affiliation(s)
- Rafael Ramirez-Carracedo
- Unidad Mixta de Investigación Cardiovascular, Departamento de Cardiología, Universidad Francisco de Vitoria, Hospital Ramón y Cajal (IRYCIS), Madrid, Spain (R.R.-C., I.H., L.T., J.D.-M., L.B., C.Z.).,Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III (ISCIII), Madrid, Spain (R.R.-C., M. Sanmartin, I.H., L.T., M. Saura, J.L.Z., C.Z.)
| | - Marcelo Sanmartin
- Departamento de Cardiología, Hospital Universitario Ramón y Cajal (IRYCIS), Madrid, Spain (M. Sanmartin, J.L.Z.).,Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III (ISCIII), Madrid, Spain (R.R.-C., M. Sanmartin, I.H., L.T., M. Saura, J.L.Z., C.Z.)
| | - Amadeo Ten
- Instituto de Investigación de salud La Fe, Grupo de Investigación Biomédica (GIBI230-PREBI). Nodo de Imagen La Fe en la Red de Imagen Biomédica (ReDIB) de Infraestructuras Científicas Técnicas y Singulares (ICTS), Valencia, Spain (A.T., L.M.-B.)
| | - Ignacio Hernandez
- Unidad Mixta de Investigación Cardiovascular, Departamento de Cardiología, Universidad Francisco de Vitoria, Hospital Ramón y Cajal (IRYCIS), Madrid, Spain (R.R.-C., I.H., L.T., J.D.-M., L.B., C.Z.).,Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III (ISCIII), Madrid, Spain (R.R.-C., M. Sanmartin, I.H., L.T., M. Saura, J.L.Z., C.Z.)
| | - Laura Tesoro
- Unidad Mixta de Investigación Cardiovascular, Departamento de Cardiología, Universidad Francisco de Vitoria, Hospital Ramón y Cajal (IRYCIS), Madrid, Spain (R.R.-C., I.H., L.T., J.D.-M., L.B., C.Z.)
| | - Javier Diez-Mata
- Unidad Mixta de Investigación Cardiovascular, Departamento de Cardiología, Universidad Francisco de Vitoria, Hospital Ramón y Cajal (IRYCIS), Madrid, Spain (R.R.-C., I.H., L.T., J.D.-M., L.B., C.Z.)
| | - Laura Botana
- Unidad Mixta de Investigación Cardiovascular, Departamento de Cardiología, Universidad Francisco de Vitoria, Hospital Ramón y Cajal (IRYCIS), Madrid, Spain (R.R.-C., I.H., L.T., J.D.-M., L.B., C.Z.)
| | - Karina Ovejero-Paredes
- Grupo de Nanobiotecnología para Ciencias de la Vida, Departamento de Química en Ciencias Farmaceuticas Facultad de Farmacia, Universidad Complutense de Madrid (UCM). Unidad de Microscopia e Imagen Dinamica, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain (K.O.-P., M.F.)
| | - Marco Filice
- QUIBIM SL - Quantitative Imaging Biomarkers in Medicine, Valencia, Spain (A.A.-B.)
| | - Angel Alberich-Bayarri
- Departamento de Cirugía Experimental, Hospital Universitario La Paz, Madrid, Spain (C.L.-A.)
| | - Luis Martí-Bonmatí
- Instituto de Investigación de salud La Fe, Grupo de Investigación Biomédica (GIBI230-PREBI). Nodo de Imagen La Fe en la Red de Imagen Biomédica (ReDIB) de Infraestructuras Científicas Técnicas y Singulares (ICTS), Valencia, Spain (A.T., L.M.-B.)
| | - Carlota Largo-Aramburu
- Departamento de Cirugía Experimental, Hospital Universitario La Paz, Madrid, Spain (C.L.-A.)
| | - Marta Saura
- Unidad de Fisiología, Departamento de Biología de Sistemas, Universidad de Alcalá (IRYCIS), Alcalá de Henares, Madrid, Spain (M. Saura).,Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III (ISCIII), Madrid, Spain (R.R.-C., M. Sanmartin, I.H., L.T., M. Saura, J.L.Z., C.Z.)
| | - Jose Luis Zamorano
- Departamento de Cardiología, Hospital Universitario Ramón y Cajal (IRYCIS), Madrid, Spain (M. Sanmartin, J.L.Z.).,Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III (ISCIII), Madrid, Spain (R.R.-C., M. Sanmartin, I.H., L.T., M. Saura, J.L.Z., C.Z.)
| | - Carlos Zaragoza
- Unidad Mixta de Investigación Cardiovascular, Departamento de Cardiología, Universidad Francisco de Vitoria, Hospital Ramón y Cajal (IRYCIS), Madrid, Spain (R.R.-C., I.H., L.T., J.D.-M., L.B., C.Z.).,Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III (ISCIII), Madrid, Spain (R.R.-C., M. Sanmartin, I.H., L.T., M. Saura, J.L.Z., C.Z.)
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Chyu KY, Zhao X, Zhou J, Dimayuga PC, Lio NW, Cercek B, Trac NT, Chung EJ, Shah PK. Immunization using ApoB-100 peptide-linked nanoparticles reduces atherosclerosis. JCI Insight 2022; 7:149741. [PMID: 35536648 PMCID: PMC9220835 DOI: 10.1172/jci.insight.149741] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Accepted: 04/26/2022] [Indexed: 11/30/2022] Open
Abstract
Active immunization with the apolipoprotein B-100 (ApoB-100) peptide P210 reduces experimental atherosclerosis. To advance this immunization strategy to future clinical testing, we explored the possibility of delivering P210 as an antigen using nanoparticles, given this approach has been used clinically. We first characterized the responses of T cells to P210 using PBMCs from patients with atherosclerotic cardiovascular disease (ASCVD). We then investigated the use of P210 in self-assembling peptide amphiphile micelles (P210-PAMs) as a vaccine formulation to reduce atherosclerosis in B6.129P2-Apoetm1Unc/J (ApoE–/–) mice and P210’s potential mechanisms of action. We also generated and characterized a humanized mouse model with chimeric HLA-A*02:01/Kb in ApoE–/– background to test the efficacy of P210-PAM immunization as a bridge to future clinical testing. P210 provoked T cell activation and memory response in PBMCs of patients with ASCVD. Dendritic cell uptake of P210-PAM and its costaining with MHC-I molecules supported its use as a vaccine formulation. In ApoE–/– mice, immunization with P210-PAMs dampened P210-specific CD4+ T cell proliferative response and CD8+ T cell cytolytic response, modulated macrophage phenotype, and significantly reduced aortic atherosclerosis. Potential clinical relevance of P210-PAM immunization was demonstrated by reduced atherosclerosis in the humanized ApoE–/– mouse model. Our data support experimental and translational use of P210-PAM as a potential vaccine candidate against human ASCVD.
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Affiliation(s)
- Kuang-Yuh Chyu
- Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Heart Institute, Los Angeles, United States of America
| | - Xiaoning Zhao
- Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Heart Institute, Los Angeles, United States of America
| | - Jianchang Zhou
- Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Heart Institute, Los Angeles, United States of America
| | - Paul C Dimayuga
- Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Heart Institute, Los Angeles, United States of America
| | - Nicole Wm Lio
- Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Heart Institute, Los Angeles, United States of America
| | - Bojan Cercek
- Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Heart Institute, Los Angeles, United States of America
| | - Noah T Trac
- Department of Biomedical Engineering, University of Southern California, Los Angeles, United States of America
| | - Eun Ji Chung
- Department of Biomedical Engineering, University of Southern California, Los Angeles, United States of America
| | - Prediman K Shah
- Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Heart Institute, Los Angeles, United States of America
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Chen L, Yang J, Fu X, Huang W, Yu X, Leng F, Yu C, Yang Z. A targeting mesoporous dopamine nanodrug platform with NIR responsiveness for atherosclerosis improvement. BIOMATERIALS ADVANCES 2022; 136:212775. [PMID: 35929293 DOI: 10.1016/j.bioadv.2022.212775] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Revised: 03/07/2022] [Accepted: 03/21/2022] [Indexed: 05/27/2023]
Abstract
Atherosclerosis (AS), the formation of plaque lesions in the walls of arteries, causes many mortalities and morbidities worldwide. Currently, achieving site-specific delivery and controlled release at plaques is difficult. Herein, we implemented the strategy of constructing a bionic multifunctional nanoplatform (BM-NP) for targeting and improving plaques. BM-NPs were prepared based on probucol-loaded mesoporous polydopamine (MPDA) carriers and were coated with platelet membranes to impart bionic properties. In vitro experiments confirmed that BM-NPs, which respond to near-infrared (NIR) for drug release, remove reactive oxygen species (ROS), thereby reducing the level of oxidized low-density lipoprotein (ox-LDL) and ultimately helping to inhibit macrophage foaming. In vivo experiments proved that BM-NPs actively accumulated in plaques in the mouse right carotid artery (RCA) ligation model. During treatment, BM-NPs with NIR laser irradiation more effectively reduced the area of plaque deposition and slowed the thickening of the arterial wall intima. More importantly, BM-NPs showed the advantage of inhibiting the increase in triglyceride (TG) content in the body, and good biocompatibility. Hence, our research results indicate that intelligent BM-NPs can be used as a potential nanotherapy to precisely and synergistically improve AS.
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Affiliation(s)
- Lu Chen
- College of Pharmacy, Chongqing Key Laboratory for Pharmaceutical Metabolism Research, Chongqing pharmacodynamic evaluation engineering technology research center, Chongqing 400016, China
| | - Jiaxin Yang
- College of Pharmacy, Chongqing Key Laboratory for Pharmaceutical Metabolism Research, Chongqing pharmacodynamic evaluation engineering technology research center, Chongqing 400016, China
| | - Xiaoxue Fu
- College of Pharmacy, Chongqing Key Laboratory for Pharmaceutical Metabolism Research, Chongqing pharmacodynamic evaluation engineering technology research center, Chongqing 400016, China
| | - Wenyan Huang
- College of Pharmacy, Chongqing Key Laboratory for Pharmaceutical Metabolism Research, Chongqing pharmacodynamic evaluation engineering technology research center, Chongqing 400016, China
| | - Xiaojuan Yu
- College of Pharmacy, Chongqing Key Laboratory for Pharmaceutical Metabolism Research, Chongqing pharmacodynamic evaluation engineering technology research center, Chongqing 400016, China
| | - Feng Leng
- College of Pharmacy, Chongqing Key Laboratory for Pharmaceutical Metabolism Research, Chongqing pharmacodynamic evaluation engineering technology research center, Chongqing 400016, China
| | - Chao Yu
- College of Pharmacy, Chongqing Key Laboratory for Pharmaceutical Metabolism Research, Chongqing pharmacodynamic evaluation engineering technology research center, Chongqing 400016, China.
| | - Zhangyou Yang
- College of Pharmacy, Chongqing Key Laboratory for Pharmaceutical Metabolism Research, Chongqing pharmacodynamic evaluation engineering technology research center, Chongqing 400016, China.
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42
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Zhang X, Liu W. Engineering Injectable Anti‐Inflammatory Hydrogels to Treat Acute Myocardial Infarction. ADVANCED NANOBIOMED RESEARCH 2022. [DOI: 10.1002/anbr.202200008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Affiliation(s)
- Xiaoping Zhang
- Tianjin Key Laboratory of Composite and Functional Materials School of Material Science and Engineering Tianjin University Tianjin 300350 China
| | - Wenguang Liu
- Tianjin Key Laboratory of Composite and Functional Materials School of Material Science and Engineering Tianjin University Tianjin 300350 China
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Aprotosoaie AC, Costache AD, Costache II. Therapeutic Strategies and Chemoprevention of Atherosclerosis: What Do We Know and Where Do We Go? Pharmaceutics 2022; 14:722. [PMID: 35456556 PMCID: PMC9025701 DOI: 10.3390/pharmaceutics14040722] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Revised: 03/24/2022] [Accepted: 03/26/2022] [Indexed: 12/15/2022] Open
Abstract
Despite progress in understanding the pathogenesis of atherosclerosis, the development of effective therapeutic strategies is a challenging task that requires more research to attain its full potential. This review discusses current pharmacotherapy in atherosclerosis and explores the potential of some important emerging therapies (antibody-based therapeutics, cytokine-targeting therapy, antisense oligonucleotides, photodynamic therapy and theranostics) in terms of clinical translation. A chemopreventive approach based on modern research of plant-derived products is also presented. Future perspectives on preventive and therapeutic management of atherosclerosis and the design of tailored treatments are outlined.
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Affiliation(s)
- Ana Clara Aprotosoaie
- Faculty of Pharmacy, Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania;
| | - Alexandru-Dan Costache
- Department of Cardiovascular Rehabilitation, Clinical Rehabilitation Hospital, 700661 Iasi, Romania
- Department of Internal Medicine I, Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iasi, Romania;
| | - Irina-Iuliana Costache
- Department of Internal Medicine I, Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iasi, Romania;
- Department of Cardiology, “St. Spiridon” Emergency County Hospital, 700111 Iasi, Romania
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Li L, Liu S, Tan J, Wei L, Wu D, Gao S, Weng Y, Chen J. Recent advance in treatment of atherosclerosis: Key targets and plaque-positioned delivery strategies. J Tissue Eng 2022; 13:20417314221088509. [PMID: 35356091 PMCID: PMC8958685 DOI: 10.1177/20417314221088509] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Atherosclerosis, a chronic inflammatory disease of vascular wall, is a progressive pathophysiological process with lipids oxidation/depositing initiation and innate/adaptive immune responses. The coordination of multi systems covering oxidative stress, dysfunctional endothelium, diseased lipid uptake, cell apoptosis, thrombotic and pro-inflammatory responding as well as switched SMCs contributes to plaque growth. In this circumstance, inevitably, targeting these processes is considered to be effective for treating atherosclerosis. Arriving, retention and working of payload candidates mediated by targets in lesion direct ultimate therapeutic outcomes. Accumulating a series of scientific studies and clinical practice in the past decades, lesion homing delivery strategies including stent/balloon/nanoparticle-based transportation worked as the potent promotor to ensure a therapeutic effect. The objective of this review is to achieve a very brief summary about the effective therapeutic methods cooperating specifical targets and positioning-delivery strategies in atherosclerosis for better outcomes.
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Affiliation(s)
- Li Li
- Key Laboratory of Advanced Technology of Materials, Ministry of Education, Southwest Jiaotong University, Chengdu, PR China
| | - Sainan Liu
- Key Laboratory of Advanced Technology of Materials, Ministry of Education, Southwest Jiaotong University, Chengdu, PR China
| | - Jianying Tan
- Key Laboratory of Advanced Technology of Materials, Ministry of Education, Southwest Jiaotong University, Chengdu, PR China
| | - Lai Wei
- Key Laboratory of Advanced Technology of Materials, Ministry of Education, Southwest Jiaotong University, Chengdu, PR China
| | - Dimeng Wu
- Chengdu Daxan Innovative Medical Tech. Co., Ltd., Chengdu, PR China
| | - Shuai Gao
- Chengdu Daxan Innovative Medical Tech. Co., Ltd., Chengdu, PR China
| | - Yajun Weng
- Key Laboratory of Advanced Technology of Materials, Ministry of Education, Southwest Jiaotong University, Chengdu, PR China
| | - Junying Chen
- Key Laboratory of Advanced Technology of Materials, Ministry of Education, Southwest Jiaotong University, Chengdu, PR China
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Wu Z, Wu R, Li X, Wang X, Tang X, Tan K, Wan M, Mao C, Xu X, Jiang H, Li J, Zhou M, Shi D. Multi-Pathway Microenvironment Regulation for Atherosclerosis Therapy Based on Beta-Cyclodextrin/L-Arginine/Au Nanomotors with Dual-Mode Propulsion. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2022; 18:e2104120. [PMID: 34918450 DOI: 10.1002/smll.202104120] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/30/2021] [Revised: 11/23/2021] [Indexed: 06/14/2023]
Abstract
Most of the current non-pharmacological treatment strategies for atherosclerosis (AS) suffer from poor penetration into the plaque and only aim at a certain factor in its formation process, resulting in limited therapeutic effect. Herein, a kind of nanomotor with dual-mode propulsion is constructed, which is sensitive to higher reactive oxygen species (ROS) at the AS site and near-infrared (NIR) laser by the covalent binding and self-assembly of β-cyclodextrin (β-CD) and L-arginine (LA) with immobilization of Au nanoparticles. NIR laser irradiation can be used as a driving force and to ablate inflammatory macrophages through the photothermal effect. The nitric oxide (NO) released by the nanomotors can be used as another driving force and a therapeutic agent to promote endothelial repair in the plaque site. LA can eliminate ROS in the inflammatory site, and β-CD can promote the removal of cholesterol from foam cells. In particular, the two driving modes of nanomotors synergistically promote their aggregation and penetration in the plaque. This kind of nanomotor can regulate the microenvironment of AS in multiple ways, including combination therapy for endothelial repair, lipid clearance, and reducing ROS, which is expected to become a potential non-pharmacological strategy in the treatment of AS.
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Affiliation(s)
- Ziyu Wu
- Department of Vascular Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China
| | - Rui Wu
- State Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China
| | - Xiaoyun Li
- National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing, 210023, China
| | - Xingwen Wang
- National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing, 210023, China
| | - Xueting Tang
- National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing, 210023, China
| | - Kaiyuan Tan
- National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing, 210023, China
| | - Mimi Wan
- National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing, 210023, China
| | - Chun Mao
- National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing, 210023, China
| | - Xingquan Xu
- State Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China
| | - Huiming Jiang
- State Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China
| | - Jiawei Li
- State Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China
| | - Min Zhou
- Department of Vascular Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China
| | - Dongquan Shi
- State Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China
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46
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Simultaneous Noninvasive Detection and Therapy of Atherosclerosis Using HDL Coated Gold Nanorods. Diagnostics (Basel) 2022; 12:diagnostics12030577. [PMID: 35328130 PMCID: PMC8947645 DOI: 10.3390/diagnostics12030577] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Revised: 02/20/2022] [Accepted: 02/21/2022] [Indexed: 11/20/2022] Open
Abstract
Cardiovascular disease (CVD) is a major cause of death and disability worldwide. A real need exists in the development of new, improved therapeutic methods for treating CVD, while major advances in nanotechnology have opened new avenues in this field. In this paper, we report the use of gold nanoparticles (GNPs) coated with high-density lipoprotein (HDL) (GNP-HDL) for the simultaneous detection and therapy of unstable plaques. Based on the well-known HDL cardiovascular protection, by promoting the reverse cholesterol transport (RCT), injured rat carotids, as a model for unstable plaques, were injected with the GNP-HDL. Noninvasive detection of the plaques 24 h post the GNP injection was enabled using the diffusion reflection (DR) method, indicating that the GNP-HDL particles had accumulated in the injured site. Pathology and noninvasive CT measurements proved the recovery of the injured artery treated with the GNP-HDL. The DR of the GNP-HDL presented a simple and highly sensitive method at a low cost, resulting in simultaneous specific unstable plaque diagnosis and recovery.
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47
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Nanomaterials as Ultrasound Theragnostic Tools for Heart Disease Treatment/Diagnosis. Int J Mol Sci 2022; 23:ijms23031683. [PMID: 35163604 PMCID: PMC8835969 DOI: 10.3390/ijms23031683] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 01/25/2022] [Accepted: 01/26/2022] [Indexed: 01/27/2023] Open
Abstract
A variety of different nanomaterials (NMs) such as microbubbles (MBs), nanobubbles (NBs), nanodroplets (NDs), and silica hollow meso-structures have been tested as ultrasound contrast agents for the detection of heart diseases. The inner part of these NMs is made gaseous to yield an ultrasound contrast, which arises from the difference in acoustic impedance between the interior and exterior of such a structure. Furthermore, to specifically achieve a contrast in the diseased heart region (DHR), NMs can be designed to target this region in essentially three different ways (i.e., passively when NMs are small enough to diffuse through the holes of the vessels supplying the DHR, actively by being associated with a ligand that recognizes a receptor of the DHR, or magnetically by applying a magnetic field orientated in the direction of the DHR on a NM responding to such stimulus). The localization and resolution of ultrasound imaging can be further improved by applying ultrasounds in the DHR, by increasing the ultrasound frequency, or by using harmonic, sub-harmonic, or super-resolution imaging. Local imaging can be achieved with other non-gaseous NMs of metallic composition (i.e., essentially made of Au) by using photoacoustic imaging, thus widening the range of NMs usable for cardiac applications. These contrast agents may also have a therapeutic efficacy by carrying/activating/releasing a heart disease drug, by triggering ultrasound targeted microbubble destruction or enhanced cavitation in the DHR, for example, resulting in thrombolysis or helping to prevent heart transplant rejection.
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49
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Sheng J, Zu Z, Zhang Y, Zhu H, Qi J, Zheng T, Tian Y, Zhang L. Targeted therapy of atherosclerosis by zeolitic imidazolate framework-8 nanoparticles loaded with losartan potassium via simultaneous lipid-scavenging and anti-inflammation. J Mater Chem B 2022; 10:5925-5937. [PMID: 35639392 DOI: 10.1039/d2tb00686c] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Atherosclerosis (AS) is a condition associated with dysfunctional lipid metabolism and an inflammatory immune microenvironment that remains the leading cause of severe cardiovascular events. Drugs exhibiting both anti-inflammatory and lipid-scavenging...
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Affiliation(s)
- Jie Sheng
- Department of Radiology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, China
| | - Ziyue Zu
- Department of Radiology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, China
| | - Yugang Zhang
- State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Centre of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China
| | - Haitao Zhu
- Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, 212001, China
| | - Jianchen Qi
- Department of Radiology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, China
| | - Tao Zheng
- Department of Radiology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, China
| | - Ying Tian
- Department of Radiology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, China
| | - Longjiang Zhang
- Department of Radiology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, China
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Paluszkiewicz P, Martuszewski A, Zaręba N, Wala K, Banasik M, Kepinska M. The Application of Nanoparticles in Diagnosis and Treatment of Kidney Diseases. Int J Mol Sci 2021; 23:ijms23010131. [PMID: 35008556 PMCID: PMC8745391 DOI: 10.3390/ijms23010131] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Revised: 12/16/2021] [Accepted: 12/21/2021] [Indexed: 12/12/2022] Open
Abstract
Nanomedicine is currently showing great promise for new methods of diagnosing and treating many diseases, particularly in kidney disease and transplantation. The unique properties of nanoparticles arise from the diversity of size effects, used to design targeted nanoparticles for specific cells or tissues, taking renal clearance and tubular secretion mechanisms into account. The design of surface particles on nanoparticles offers a wide range of possibilities, among which antibodies play an important role. Nanoparticles find applications in encapsulated drug delivery systems containing immunosuppressants and other drugs, in imaging, gene therapies and many other branches of medicine. They have the potential to revolutionize kidney transplantation by reducing and preventing ischemia-reperfusion injury, more efficiently delivering drugs to the graft site while avoiding systemic effects, accurately localizing and visualising the diseased site and enabling continuous monitoring of graft function. So far, there are known nanoparticles with no toxic effects on human tissue, although further studies are still needed to confirm their safety.
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Affiliation(s)
- Patrycja Paluszkiewicz
- Department of Emergency Medical Service, Wroclaw Medical University, Bartla 5, 50-367 Wroclaw, Poland;
| | - Adrian Martuszewski
- Department of Population Health, Division of Environmental Health and Occupational Medicine, Wroclaw Medical University, Mikulicza-Radeckiego 7, 50-368 Wroclaw, Poland;
| | - Natalia Zaręba
- Department of Pharmaceutical Biochemistry, Division of Biomedical and Environmental Analysis, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211a, 50-556 Wrocław, Poland;
| | - Kamila Wala
- Faculty of Medicine, Wroclaw Medical University, Pasteura 1, 50-367 Wroclaw, Poland;
| | - Mirosław Banasik
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland
- Correspondence: (M.B.); (M.K.); Tel.: +48-71-733-2500 (M.B.); +48-71-784-0171 (M.K.)
| | - Marta Kepinska
- Department of Pharmaceutical Biochemistry, Division of Biomedical and Environmental Analysis, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211a, 50-556 Wrocław, Poland;
- Correspondence: (M.B.); (M.K.); Tel.: +48-71-733-2500 (M.B.); +48-71-784-0171 (M.K.)
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