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Molon AC, Heguedusch D, Nunes FD, Cecatto RB, Dos Santos Franco AL, de Oliveira Rodini Pegoraro C, Rodrigues MFSD. A 5-ALA mediated photodynamic therapy increases natural killer cytotoxicity against oral squamous cell carcinoma cell lines. JOURNAL OF BIOPHOTONICS 2024:e202400176. [PMID: 39023037 DOI: 10.1002/jbio.202400176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Revised: 06/03/2024] [Accepted: 06/25/2024] [Indexed: 07/20/2024]
Abstract
Oral squamous cell carcinoma (OSCC) constitutes over 90% of oral cancers, known for its aggressiveness and poor prognosis. Photodynamic therapy (PDT) has emerged as a promising adjuvant therapy and is linked to immunogenic cell death, activating innate and adaptive anti-tumor responses. Natural Killer (NK) cells, key players in malignant cell elimination, have not been extensively studied in PDT. This study evaluates whether PDT increases OSCC cell lines' susceptibility to NK cell cytotoxicity. PDT, using 5-aminolevulinic acid (5-ALA) and LED irradiation, was applied to Ca1 and Luc4 cell lines. Results showed a dose-dependent viability decrease post-PDT. Gene expression analysis revealed upregulation of NK cell-activating ligands (ULBP1-4, MICA/B) and decreased MHC class I expression in Ca1, suggesting increased NK cell susceptibility. Enhanced NK cell cytotoxicity was confirmed in Ca1 but not in Luc4 cells. These findings indicate that PDT may enhance NK cell-mediated cytotoxicity in OSCC, offering potential for improved treatment strategies.
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Affiliation(s)
- Angela Cristina Molon
- Post Graduate Program in Biophotonics Applied to Health Sciences, Nove de Julho University, São Paulo, Brazil
| | - Daniele Heguedusch
- Department of Stomatology, Discipline of Oral and Maxillofacial Pathology, School of Dentistry, University of São Paulo, São Paulo, Brazil
| | - Fabio Daumas Nunes
- Department of Stomatology, Discipline of Oral and Maxillofacial Pathology, School of Dentistry, University of São Paulo, São Paulo, Brazil
| | - Rebeca Boltes Cecatto
- Post Graduate Program in Biophotonics Applied to Health Sciences, Nove de Julho University, São Paulo, Brazil
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2
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Deng W, Shang H, Tong Y, Liu X, Huang Q, He Y, Wu J, Ba X, Chen Z, Chen Y, Tang K. The application of nanoparticles-based ferroptosis, pyroptosis and autophagy in cancer immunotherapy. J Nanobiotechnology 2024; 22:97. [PMID: 38454419 PMCID: PMC10921615 DOI: 10.1186/s12951-024-02297-8] [Citation(s) in RCA: 19] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Accepted: 01/02/2024] [Indexed: 03/09/2024] Open
Abstract
Immune checkpoint blockers (ICBs) have been applied for cancer therapy and achieved great success in the field of cancer immunotherapy. Nevertheless, the broad application of ICBs is limited by the low response rate. To address this issue, increasing studies have found that the induction of immunogenic cell death (ICD) in tumor cells is becoming an emerging therapeutic strategy in cancer treatment, not only straightly killing tumor cells but also enhancing dying cells immunogenicity and activating antitumor immunity. ICD is a generic term representing different cell death modes containing ferroptosis, pyroptosis, autophagy and apoptosis. Traditional chemotherapeutic agents usually inhibit tumor growth based on the apoptotic ICD, but most tumor cells are resistant to the apoptosis. Thus, the induction of non-apoptotic ICD is considered to be a more efficient approach for cancer therapy. In addition, due to the ineffective localization of ICD inducers, various types of nanomaterials have been being developed to achieve targeted delivery of therapeutic agents and improved immunotherapeutic efficiency. In this review, we briefly outline molecular mechanisms of ferroptosis, pyroptosis and autophagy, as well as their reciprocal interactions with antitumor immunity, and then summarize the current progress of ICD-induced nanoparticles based on different strategies and illustrate their applications in the cancer therapy.
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Affiliation(s)
- Wen Deng
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Haojie Shang
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Yonghua Tong
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Xiao Liu
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Qiu Huang
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Yu He
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Jian Wu
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Xiaozhuo Ba
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Zhiqiang Chen
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Yuan Chen
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
- Department of Geriatric Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
| | - Kun Tang
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
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3
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Zare A, Shamshiripour P, Lotfi S, Shahin M, Rad VF, Moradi AR, Hajiahmadi F, Ahmadvand D. Clinical theranostics applications of photo-acoustic imaging as a future prospect for cancer. J Control Release 2022; 351:805-833. [DOI: 10.1016/j.jconrel.2022.09.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 09/07/2022] [Accepted: 09/09/2022] [Indexed: 10/31/2022]
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Younis MR, He G, Qu J, Lin J, Huang P, Xia X. Inorganic Nanomaterials with Intrinsic Singlet Oxygen Generation for Photodynamic Therapy. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2021; 8:e2102587. [PMID: 34561971 PMCID: PMC8564446 DOI: 10.1002/advs.202102587] [Citation(s) in RCA: 58] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Revised: 08/22/2021] [Indexed: 05/07/2023]
Abstract
Inorganic nanomaterials with intrinsic singlet oxygen (1 O2 ) generation capacity, are emerged yet dynamically developing materials as nano-photosensitizers (NPSs) for photodynamic therapy (PDT). Compared to previously reported nanomaterials that have been used as either carriers to load organic PSs or energy donors to excite the attached organic PSs through a Foster resonance energy transfer process, these NPSs possess intrinsic 1 O2 generation capacity with extremely high 1 O2 quantum yield (e.g., 1.56, 1.3, 1.26, and 1.09) than any classical organic PS reported to date, and thus are facilitating to make a revolution in PDT. In this review, the recent advances in the development of various inorganic nanomaterials as NPSs, including metal-based (gold, silver, and tungsten), metal oxide-based (titanium dioxide, tungsten oxide, and bismuth oxyhalide), metal sulfide-based (copper and molybdenum sulfide), carbon-based (graphene, fullerene, and graphitic carbon nitride), phosphorus-based, and others (hybrids and MXenes-based NPSs) are summarized, with an emphasis on the design principle and 1 O2 generation mechanism, and the photodynamic therapeutic performance against different types of cancers. Finally, the current challenges and an outlook of future research are also discussed. This review may provide a comprehensive account capable of explaining recent progress as well as future research of this emerging paradigm.
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Affiliation(s)
- Muhammad Rizwan Younis
- Marshall Laboratory of Biomedical EngineeringInternational Cancer CenterLaboratory of Evolutionary Theranostics (LET)School of Biomedical EngineeringShenzhen University Health Science CenterShenzhen518060China
- Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong ProvinceCollege of Optoelectronic EngineeringShenzhen UniversityShenzhen518060China
- State Key Laboratory of Analytical Chemistry for Life Science and Collaborative Innovation Center of Chemistry for Life SciencesSchool of Chemistry and Chemical EngineeringNanjing UniversityNanjing210093P.R. China
| | - Gang He
- Marshall Laboratory of Biomedical EngineeringInternational Cancer CenterLaboratory of Evolutionary Theranostics (LET)School of Biomedical EngineeringShenzhen University Health Science CenterShenzhen518060China
| | - Junle Qu
- Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong ProvinceCollege of Optoelectronic EngineeringShenzhen UniversityShenzhen518060China
| | - Jing Lin
- Marshall Laboratory of Biomedical EngineeringInternational Cancer CenterLaboratory of Evolutionary Theranostics (LET)School of Biomedical EngineeringShenzhen University Health Science CenterShenzhen518060China
| | - Peng Huang
- Marshall Laboratory of Biomedical EngineeringInternational Cancer CenterLaboratory of Evolutionary Theranostics (LET)School of Biomedical EngineeringShenzhen University Health Science CenterShenzhen518060China
| | - Xing‐Hua Xia
- State Key Laboratory of Analytical Chemistry for Life Science and Collaborative Innovation Center of Chemistry for Life SciencesSchool of Chemistry and Chemical EngineeringNanjing UniversityNanjing210093P.R. China
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5
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Wang S, Tian R, Zhang X, Cheng G, Yu P, Chang J, Chen X. Beyond Photo: Xdynamic Therapies in Fighting Cancer. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2021; 33:e2007488. [PMID: 33987898 DOI: 10.1002/adma.202007488] [Citation(s) in RCA: 58] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Revised: 12/02/2020] [Indexed: 05/14/2023]
Abstract
Reactive oxygen species (ROS)-related therapeutic approaches are developed as a promising modality for cancer treatment because the aberrant increase of intracellular ROS level can cause cell death due to nonspecific oxidation damage to key cellular biomolecules. However, the most widely considered strategy, photodynamic therapy (PDT), suffers from critical limitations such as limited tissue-penetration depth, high oxygen dependence, and phototoxicity. Non-photo-induced ROS generation strategies, which are defined as Xdynamic therapies (X = sono, radio, microwave, chemo, thermo, and electro), show good potential to overcome the drawbacks of PDT. Herein, recent advances in the development of Xdynamic therapies, including the design of systems, the working mechanisms, and examples of cancer therapy application, are introduced. Furthermore, the approaches to enhance treatment efficiency of Xdynamic therapy are highlighted. Finally, the perspectives and challenges of these strategies are also discussed.
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Affiliation(s)
- Sheng Wang
- School of Life Sciences, Tianjin University, Tianjin, 300072, China
| | - Rui Tian
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102, China
| | - Xu Zhang
- School of Life Sciences, Tianjin University, Tianjin, 300072, China
| | - Guohui Cheng
- School of Life Sciences, Tianjin University, Tianjin, 300072, China
| | - Peng Yu
- School of Life Sciences, Tianjin University, Tianjin, 300072, China
| | - Jin Chang
- School of Life Sciences, Tianjin University, Tianjin, 300072, China
| | - Xiaoyuan Chen
- Departments of Diagnostic Radiology and Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore
- Departments of Chemical and Biomolecular Engineering, and, Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore, 117597, Singapore
- Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore
- Nanomedicine Translational Research Program, NUS Center for Nanomedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore
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Zou M, Zhao Y, Ding B, Jiang F, Chen Y, Ma P, Lin J. NIR-triggered biodegradable MOF-coated upconversion nanoparticles for synergetic chemodynamic/photodynamic therapy with enhanced efficacy. Inorg Chem Front 2021. [DOI: 10.1039/d1qi00252j] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The generation of reactive oxygen species (ROS) is often limited by the overexpression of glutathione (GSH) in the tumor microenvironment (TME) and the penetration depth of visible light.
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Affiliation(s)
- Man Zou
- School of Applied Physics and Materials
- Wuyi University
- Jiangmen 529020
- P. R. China
- State Key Laboratory of Rare Earth Resource Utilization
| | - Yajie Zhao
- State Key Laboratory of Rare Earth Resource Utilization
- Changchun Institute of Applied Chemistry
- Chinese Academy of Sciences
- Changchun 130022
- P. R. China
| | - Binbin Ding
- State Key Laboratory of Rare Earth Resource Utilization
- Changchun Institute of Applied Chemistry
- Chinese Academy of Sciences
- Changchun 130022
- P. R. China
| | - Fan Jiang
- State Key Laboratory of Rare Earth Resource Utilization
- Changchun Institute of Applied Chemistry
- Chinese Academy of Sciences
- Changchun 130022
- P. R. China
| | - Yeqing Chen
- School of Applied Physics and Materials
- Wuyi University
- Jiangmen 529020
- P. R. China
| | - Ping'an Ma
- State Key Laboratory of Rare Earth Resource Utilization
- Changchun Institute of Applied Chemistry
- Chinese Academy of Sciences
- Changchun 130022
- P. R. China
| | - Jun Lin
- School of Applied Physics and Materials
- Wuyi University
- Jiangmen 529020
- P. R. China
- State Key Laboratory of Rare Earth Resource Utilization
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7
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Lin X, Cao Y, Xue Y, Wu F, Yu F, Wu M, Zhu X. Multifunctional theranostic agents based on prussian blue nanoparticles for tumor targeted and MRI-guided photodynamic/photothermal combined treatment. NANOTECHNOLOGY 2020; 31:135101. [PMID: 31783383 DOI: 10.1088/1361-6528/ab5d84] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/25/2023]
Abstract
The independence of photodynamic or photothermal modality create difficulties in the success of tumor therapy. In this current study, a multifunctional nanotheranostic agent of PDE-Ce6-HA was developed for tumor targeted and MRI-guided photodynamic/photothermal combined therapy (PDT/PTT). For this purpose, the near-infrared-absorbing nanoparticles of prussian blue were coated with polydopamine and successively conjugated with chlorin e6 (Ce6) for reactive oxygen species (ROS) generation. The resultant nanoparticles, denoted as PDE-Ce6, were then modified with hyaluronic acid (HA) through electrostatic interaction to yield the final therapeutic agent of PDE-Ce6-HA NPs. PDE-Ce6-HA NPs not only exhibited high colloid stability, good biocompatibility and suitable transverse relaxation rate (0.54 mM-1 s-1), but also high photothermal conversion efficiency (40.4%) and excellent ROS generation efficiency under NIR light irradiation. The confocal microscopy images demonstrated a selective uptake of PDE-Ce6-HA by CD44 overexpressed HeLa cells via HA-mediated endocytosis. Meanwhile, in vitro anti-cancer evaluation verified the significant photodynamic and photothermal combined effects of PDE-Ce6-HA on cancer cells. Moreover, PDE-Ce6-HA led to an increase of T1-MRI contrast in tumor site. Furthermore, in vivo anti-tumor evaluation proved that the PDE-Ce6-HA under both 808 and 670 nm laser showed significantly high tumor growth inhibition effects compared with individual PTT or PDT. Hence, PDE-Ce6-HA is applicable in tumor targeted and MRI-guided photodynamic/photothermal combined treatment.
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Affiliation(s)
- Xiao Lin
- Key Laboratory for Green Chemical Process of Ministry of Education, Hubei Key Laboratory for Novel Reactor and Green Chemistry Technology, Hubei Engineering Research Center for Advanced Fine Chemicals, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan 430205, People's Republic of China
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8
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Phutim-Mangkhalthon A, Teerakapong A, Tippayawat P, Morales NP, Morkmued S, Puasiri S, Priprem A, Damrongrungruang T. Anti-inflammatory effect of photodynamic therapy using guaiazulene and red lasers on peripheral blood mononuclear cells. Photodiagnosis Photodyn Ther 2020; 31:101747. [PMID: 32200021 DOI: 10.1016/j.pdpdt.2020.101747] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Revised: 02/18/2020] [Accepted: 03/16/2020] [Indexed: 11/16/2022]
Abstract
INTRODUCTION Photodynamic therapy improves oral mucositis treatment. The reactive oxygen species (ROS) generated from this reaction could contribute to an anti-inflammatory effect by suppressing inflammatory cells. OBJECTIVE To evaluate the anti-inflammatory effect of photodynamic therapy using guaiazulene and a red laser in peripheral blood mononuclear cells (PBMCs). METHODS Guaiazulene solutions (1, 2, 5, 25, 35, and 100 μM in 99.8 % methanol) were irradiated with red laser light (625 nm, 146.2 mW/cm2) in continuous mode at 0, 4, and 8 J/cm2 in black 96-well plates. ROS were measured using spin trapping technique with electron spin resonance (ESR) spectroscopy and fluorescence. The two highest concentrations were tested using cell viability (PrestoBlue®) and anti-inflammation (RANTES and PGE2 ELISA) assay kits. Kruskal-Wallis and Dunn Bonferroni tests were used for statistical analyses with significant differences at p-value < 0.05. RESULTS Guaiazulene solutions between 2 and 5 μM exposed to red laser light at 4-8 J/cm2 generated significantly more singlet oxygen compared to the no guaiazulene group (p < 0.01) and reduced RANTES and PGE2 levels in TNF-α-inflamed peripheral blood mononuclear cells without affecting cell viability. CONCLUSION Photodynamic activation of guaiazulene generated singlet oxygen and suppressed inflammatory markers in PBMCs.
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Affiliation(s)
- Ampika Phutim-Mangkhalthon
- Division of Paediatric Dentistry, Department of Preventive Dentistry, Faculty of Dentistry, Khon Kaen University, 40002, Thailand.
| | - Aroon Teerakapong
- Division of Periodontology, Department of Oral Biomedical Sciences, Faculty of Dentistry, Khon Kaen University, 40002, Thailand; Lasers in Dentistry Research Group, Khon Kaen University, Thailand
| | - Patcharaporn Tippayawat
- Department of Clinical Chemistry, Faculty of Associated Medical Sciences, Khon Kaen University, 40002, Thailand.
| | | | - Supawich Morkmued
- Division of Paediatric Dentistry, Department of Preventive Dentistry, Faculty of Dentistry, Khon Kaen University, 40002, Thailand.
| | - Subin Puasiri
- Department of Dental Public Health, Faculty of Dentistry, Khon Kaen University, 40002, Thailand.
| | - Aroonsri Priprem
- Melatonin Research Group and Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Khon Kaen University, 40002, Thailand.
| | - Teerasak Damrongrungruang
- Division of Oral Diagnosis, Department of Oral Biomedical Science, Faculty of Dentistry, Khon Kaen University, 40002, Thailand; Lasers in Dentistry Research Group, Khon Kaen University, Thailand.
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Kielbik A, Wawryka P, Przystupski D, Rossowska J, Szewczyk A, Saczko J, Kulbacka J, Chwiłkowska A. Effects of Photosensitization of Curcumin in Human Glioblastoma Multiforme Cells. In Vivo 2020; 33:1857-1864. [PMID: 31662513 DOI: 10.21873/invivo.11679] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2019] [Revised: 08/05/2019] [Accepted: 08/07/2019] [Indexed: 12/21/2022]
Abstract
BACKGROUND/AIM There is no satisfactory treatment of glioblastoma multiforme, a highly invasive brain tumor. The aim of this study was to analyze the cytotoxic effects of curcumin (CUR) alone and as a photosensitizer on glioblastoma cells. MATERIALS AND METHODS The SNB-19 cells where incubated for 2 and 24 h with 5-200 mM of CUR. The cells were radiated with blue light (6 J/cm2) and compared to non-irradiated ones. The effects of treatment were assessed by measuring mitochondrial activity with the MTT method and apoptosis progression by flow cytometry. To investigate CUR uptake, fluorescence imaging of cells was performed. RESULTS Photosensitization of CUR decreased the EC50 6.3 times when the incubation time was 2 h and over 90% of cells underwent apoptosis. The study of the uptake of CUR showed that during the 2 h, CUR was placed in the entire cytoplasm, and over time, its amount decreased and localized in the subcellular compartments. CONCLUSION CUR is a promising medicament that can be used as a photosensitizer in photodynamic therapy for glioma treatment.
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Affiliation(s)
| | - Piotr Wawryka
- Faculty of Medicine, Wroclaw Medical University, Wroclaw, Poland
| | | | - Joanna Rossowska
- Institute of Immunology and Experimental Therapy Polish Academy of Sciences, Wroclaw, Poland
| | - Anna Szewczyk
- Department of Molecular and Cellular Biology, Wroclaw Medical University, Wroclaw, Poland.,Department of Animal Developmental Biology, Institute of Experimental Biology, University of Wroclaw, Wroclaw, Poland
| | - Jolanta Saczko
- Department of Molecular and Cellular Biology, Wroclaw Medical University, Wroclaw, Poland
| | - Julita Kulbacka
- Department of Molecular and Cellular Biology, Wroclaw Medical University, Wroclaw, Poland
| | - Agnieszka Chwiłkowska
- Department of Molecular and Cellular Biology, Wroclaw Medical University, Wroclaw, Poland
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10
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Photochemical Internalization for Intracellular Drug Delivery. From Basic Mechanisms to Clinical Research. J Clin Med 2020; 9:jcm9020528. [PMID: 32075165 PMCID: PMC7073817 DOI: 10.3390/jcm9020528] [Citation(s) in RCA: 67] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Revised: 01/14/2020] [Accepted: 02/01/2020] [Indexed: 02/06/2023] Open
Abstract
Photochemical internalisation (PCI) is a unique intervention which involves the release of endocytosed macromolecules into the cytoplasmic matrix. PCI is based on the use of photosensitizers placed in endocytic vesicles that, following light activation, lead to rupture of the endocytic vesicles and the release of the macromolecules into the cytoplasmic matrix. This technology has been shown to improve the biological activity of a number of macromolecules that do not readily penetrate the plasma membrane, including type I ribosome-inactivating proteins (RIPs), gene-encoding plasmids, adenovirus and oligonucleotides and certain chemotherapeutics, such as bleomycin. This new intervention has also been found appealing for intracellular delivery of drugs incorporated into nanocarriers and for cancer vaccination. PCI is currently being evaluated in clinical trials. Data from the first-in-human phase I clinical trial as well as an update on the development of the PCI technology towards clinical practice is presented here.
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Chen J, Fan T, Xie Z, Zeng Q, Xue P, Zheng T, Chen Y, Luo X, Zhang H. Advances in nanomaterials for photodynamic therapy applications: Status and challenges. Biomaterials 2020; 237:119827. [PMID: 32036302 DOI: 10.1016/j.biomaterials.2020.119827] [Citation(s) in RCA: 423] [Impact Index Per Article: 84.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2019] [Revised: 01/13/2020] [Accepted: 01/25/2020] [Indexed: 12/24/2022]
Abstract
Photodynamic therapy (PDT), as a non-invasive therapeutic modality that is alternative to radiotherapy and chemotherapy, is extensively investigated for cancer treatments. Although conventional organic photosensitizers (PSs) are still widely used and have achieved great progresses in PDT, the disadvantages such as hydrophobicity, poor stability within PDT environment and low cell/tissue specificity largely limit their clinical applications. Consequently, nano-agents with promising physicochemical and optical properties have emerged as an attractive alternative to overcome these drawbacks of traditional PSs. Herein, the up-to-date advances in the fabrication and fascinating applications of various nanomaterials in PDT have been summarized, including various types of nanoparticles, carbon-based nanomaterials, and two-dimensional nanomaterials, etc. In addition, the current challenges for the clinical use of PDT, and the corresponding strategies to address these issues, as well as future perspectives on further improvement of PDT have also been discussed.
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Affiliation(s)
- Jianming Chen
- Institute of Microscale Optoelectronics, Collaborative Innovation Centre for Optoelectronic Science & Technology, Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Physics and Optoelectronic Engineering, Shenzhen Key Laboratory of Micro-Nano Photonic Information Technology, Guangdong Laboratory of Artificial Intelligence and Digital Economy (SZ), Shenzhen University, Shenzhen, 518060, PR China
| | - Taojian Fan
- Institute of Microscale Optoelectronics, Collaborative Innovation Centre for Optoelectronic Science & Technology, Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Physics and Optoelectronic Engineering, Shenzhen Key Laboratory of Micro-Nano Photonic Information Technology, Guangdong Laboratory of Artificial Intelligence and Digital Economy (SZ), Shenzhen University, Shenzhen, 518060, PR China
| | - Zhongjian Xie
- Institute of Microscale Optoelectronics, Collaborative Innovation Centre for Optoelectronic Science & Technology, Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Physics and Optoelectronic Engineering, Shenzhen Key Laboratory of Micro-Nano Photonic Information Technology, Guangdong Laboratory of Artificial Intelligence and Digital Economy (SZ), Shenzhen University, Shenzhen, 518060, PR China
| | - Qiqiao Zeng
- Department of Ophthalmology, Shenzhen People's Hospital, Second Clinical Medical College of Jinan University, Shenzhen City, Guangdong Province, 518020, PR China
| | - Ping Xue
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, PR China
| | - Tingting Zheng
- Shenzhen Key Laboratory for Drug Addiction and Medication Safety, Department of Ultrasound, Peking University Shenzhen Hospital, Shenzhen, 518036, PR China
| | - Yun Chen
- Shenzhen Key Laboratory for Drug Addiction and Medication Safety, Department of Ultrasound, Peking University Shenzhen Hospital, Shenzhen, 518036, PR China
| | - Xiaoling Luo
- Department of Ophthalmology, Shenzhen People's Hospital, Second Clinical Medical College of Jinan University, Shenzhen City, Guangdong Province, 518020, PR China.
| | - Han Zhang
- Institute of Microscale Optoelectronics, Collaborative Innovation Centre for Optoelectronic Science & Technology, Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Physics and Optoelectronic Engineering, Shenzhen Key Laboratory of Micro-Nano Photonic Information Technology, Guangdong Laboratory of Artificial Intelligence and Digital Economy (SZ), Shenzhen University, Shenzhen, 518060, PR China.
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Louise Walton E. The influenza chronicles: From the 1918 pandemic to current understanding of host defense mechanisms. Biomed J 2018; 41:211-214. [PMID: 30348263 PMCID: PMC6197991 DOI: 10.1016/j.bj.2018.09.001] [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: 09/03/2018] [Accepted: 09/04/2018] [Indexed: 11/16/2022] Open
Abstract
In this special edition of the Biomedical Journal, we learn about the battle between host and influenza virus at the respiratory epithelium, and how the history of influenza pandemics has driven both major advances in the understanding of immunology and planning for future outbreaks. We also learn of a nanoparticle system that holds promise for photodynamic therapy in breast cancer. Finally, we add evidence to the debate of the safety of a minimally invasive technique for aortic valve replacement in elderly patients.
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Affiliation(s)
- Emma Louise Walton
- Staff Writer at the Biomedical Journal, 56 Dronningens gate, 7012 Trondheim, Norway.
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13
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Lesion oxygenation associates with clinical outcomes in premalignant and early stage head and neck tumors treated on a phase 1 trial of photodynamic therapy. Photodiagnosis Photodyn Ther 2017; 21:28-35. [PMID: 29113960 DOI: 10.1016/j.pdpdt.2017.10.015] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2017] [Revised: 10/06/2017] [Accepted: 10/19/2017] [Indexed: 12/16/2022]
Abstract
BACKGROUND We report on a Phase 1 trial of photodynamic therapy (PDT) for superficial head and neck (H&N) lesions. Due to known oxygen dependencies of PDT, translational measurements of lesion hemoglobin oxygen saturation (StO2) and blood volume (tHb) were studied for associations with patient outcomes. METHODS PDT with aminolevulinc acid (ALA) and escalating light doses was evaluated for high-grade dysplasia, carcinoma-in-situ, and microinvasive carcinomas of the H&N. Among 29 evaluable patients, most (18) had lesions of the tongue or floor of mouth (FOM). Disease was intact in 18 patients and present at surgical margins in 11 patients. In 26 patients, lesion StO2 and tHb was measured. RESULTS Local control (LC) at 24 months was 57.5% among all patients. In patients with tongue/FOM lesions LC was 42.7%, and it was 50.1% for those with intact lesions. Lesion tHb was not associated with 3-month complete response (CR), but StO2 was higher in patients with CR. In tongue/FOM lesions, baseline StO2 [mean(SE)] was 54(4)% in patients (n=12) with CR versus 23(8)% in patients (n=6) with local recurrence/persistence (p=0.01). Similarly, for intact disease, baseline StO2 was 54(3)% in patients (n=10) with CR versus 28(8)% in patients (n=5) without CR (p=0.03). In patients with intact disease, higher baseline StO2 associated with 24-month local control (p=0.02). CONCLUSIONS Measurement of the physiologic properties of target lesions may allow for identification of patients with the highest probability of benefiting from PDT. This provides opportunity for optimizing light delivery based on lesion characteristics and/or informing ongoing clinical decision-making in patients who would most benefit from PDT.
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Semiconducting polymer dots with photosensitizer loading and peptide modification for enhanced cell penetration and photodynamic effect. CHINESE CHEM LETT 2017. [DOI: 10.1016/j.cclet.2017.08.015] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
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15
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Could clinical photochemical internalisation be optimised to avoid neuronal toxicity? Int J Pharm 2017; 528:133-143. [PMID: 28579544 PMCID: PMC5571751 DOI: 10.1016/j.ijpharm.2017.05.071] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2017] [Revised: 05/27/2017] [Accepted: 05/29/2017] [Indexed: 01/01/2023]
Abstract
Photochemical Internalisation (PCI) is a novel drug delivery technology in which low dose photodynamic therapy (PDT) can selectively rupture endo/lysosomes by light activation of membrane-incorporated photosensitisers, facilitating intracellular drug release in the treatment of cancer. For PCI to be developed further, it is important to understand whether nerve damage is an impending side effect when treating cancers within or adjacent to nervous system tissue. Dorsal root ganglion (DRG) neurons and their associated satellite glia were subjected to PCI treatment in a 3D co-culture system following incubation with photosensitisers: meso-tetraphenylporphine (TPPS2a) or tetraphenylchlorin disulfonate (TPCS2a) and Bleomycin. Results from the use of 3D co-culture models demonstrate that a cancer cell line PCI30 and satellite glia were more sensitive to PCI than neurons and mixed glial cells, athough neurite length was affected. Neurons in culture survived PCI treatment under conditions sufficient to kill tumour cells, suggesting cancers within or adjacent to nervous system tissue could be treated with this novel technology.
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Developing a Nanoparticle-Delivered High-Efficacy Treatment for Infantile Hemangiomas Using a Mouse Hemangioendothelioma Model. Plast Reconstr Surg 2017; 138:410-417. [PMID: 27465164 DOI: 10.1097/prs.0000000000002403] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND Current treatments for infantile hemangiomas have unpredictable outcomes. The authors' aim was to develop a nanoporphyrin-delivered, high-efficacy treatment for infantile hemangiomas using a mouse hemangioendothelioma model. METHODS The authors injected mouse hemangioendothelioma cells intradermally to axillary regions of 5-week-old, female, nude mice (n = 19) to induce hemangioendothelioma growth. They documented nanoporphyrin accumulation in hemangioendotheliomas using positron emission tomography. For the treatment study, the authors randomized hemangioendothelioma-bearing nude mice (n = 9) into three groups (n = 3 each). Group I received only saline injections. Group II received only laser treatment after saline injection, and group III received laser treatment after nanoporphyrin injection through the tail vein. The authors followed up the treatment response with digital caliper measurements. RESULTS Hemangioendotheliomas started to grow approximately 1 week after inoculation and resembled infantile hemangiomas histologically. Nanoporphyrin uptake in hemangioendotheliomas was 19.7 ± 2.2, 16.7 ± 2.02, 8.4 ± 0.3, and 4.9 ± 0.6 percent injected dose per gram of tissue at 3, 6, 24, and 48 hours after injection, respectively. Nanoporphyrin uptake was significantly higher than in blood at 24 and 48 hours after injection (p < 0.05). Results of ex vivo biodistribution study were consistent with positron emission tomographic imaging. Hemangioendotheliomas in group III started to regress 1 day after the treatment and disappeared totally by day 21. The difference between tumor volumes in group III and other groups was significant on days 17 and 21 (p < 0.05). CONCLUSIONS Nanoporphyrin accumulated in hemangioendotheliomas at high concentrations, enabling a high-efficacy photodynamic therapy. Given the similarities between hemangioendotheliomas and infantile hemangiomas, this treatment potentially can be a high-efficacy treatment for infantile hemangiomas.
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Young J, Yee M, Kim H, Cheung J, Chino T, Düzgüneş N, Konopka K. Phototoxicity of Liposomal Zn- and Al-phthalocyanine Against Cervical and Oral Squamous Cell Carcinoma Cells In Vitro. Med Sci Monit Basic Res 2016; 22:156-164. [PMID: 27932777 PMCID: PMC5299971 DOI: 10.12659/msmbr.901039] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
Background Photodynamic therapy (PDT) utilizes light to activate a photosensitizer in the presence of oxygen, and leads to local photodamage by the generation of highly reactive oxygen species (ROS). Liposomal delivery of photosensitizers is adaptable to the treatment of cancers. We examined the phototoxicity of free or liposome-embedded phthalocyanine photosensitizers using HeLa cervical carcinoma and HSC-3 oral squamous cell carcinoma cells. Material/Methods Liposomes were composed of palmitoyloleoyphosphatidylcholine (POPC): phosphatidylglycerol (PG), and contained either zinc phthalocyanine (ZnPc) or aluminum phthalocyanine chloride (AlPc). Free or liposomal ZnPc and AlPc were incubated with cells for 24 h at 37°C. Cells incubated with ZnPc were exposed to broadband visible light (350–800 nm; light dose 43.2 J/cm2), whereas cells treated with AlPc were exposed to light at 690 nm (light dose 3.6 J/cm2). The effect of folate receptor-targeted liposomal ZnPc was evaluated with HeLa cells. Cytotoxicity was analyzed by the Alamar Blue assay. Results Cell viability, expressed as a percentage of control cells, was calculated according to the formula [(A570–A600) of test cells]×100/[(A570–A600) of control cells]. The relative percentage changes then defined the phototoxic efficacy of the experimental conditions. In HeLa cells, 1 μM free ZnPc and AlPc, reduced cell viability to 52.7±2.1 and 15.4±8.0%, respectively. Liposomal phthalocyanines, at 0.1, 0.5, and 1.0 μM, reduced the viability to 68.0±8.6, 15.1±9.9 and 0% (ZnPc), and to 25.8±8.2, 0 and 0% (AlPc), respectively. In HSC-3 cells, 1 μM free ZnPc and AlPc, reduced cell viability to 22.1±2.8 and 56.6±8.6%, respectively. With 1 μM liposomal ZnPc and AlPc, the viability was reduced to 0 and 21.3±0.3%, respectively. Conclusions The embedding of phthalocyanines in liposomes enhanced their phototoxicity and this effect was dependent on cell type.
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Affiliation(s)
- Jason Young
- Department of Biomedical Sciences, Arthur A. Dugoni School of Dentistry, University of the Pacific, San Francisco, USA
| | - Michael Yee
- Department of Biomedical Sciences, Arthur A. Dugoni School of Dentistry, University of the Pacific, San Francisco, USA
| | - Hayoung Kim
- Department of Biomedical Sciences, Arthur A. Dugoni School of Dentistry, University of the Pacific, San Francisco, USA
| | - Jennifer Cheung
- Department of Biomedical Sciences, Arthur A. Dugoni School of Dentistry, University of the Pacific, San Francisco, USA
| | - Takahiro Chino
- Department of Biomedical Sciences, Arthur A. Dugoni School of Dentistry, University of the Pacific, San Francisco, USA
| | - Nejat Düzgüneş
- Department of Biomedical Sciences, Arthur A. Dugoni School of Dentistry, University of the Pacific, San Francisco, USA
| | - Krystyna Konopka
- Department of Biomedical Sciences, Arthur A. Dugoni School of Dentistry, University of the Pacific, San Francisco, USA
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Rui LL, Cao HL, Xue YD, Liu LC, Xu L, Gao Y, Zhang WA. Functional organic nanoparticles for photodynamic therapy. CHINESE CHEM LETT 2016. [DOI: 10.1016/j.cclet.2016.07.011] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
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van Driel PBAA, Boonstra MC, Slooter MD, Heukers R, Stammes MA, Snoeks TJA, de Bruijn HS, van Diest PJ, Vahrmeijer AL, van Bergen En Henegouwen PMP, van de Velde CJH, Löwik CWGM, Robinson DJ, Oliveira S. EGFR targeted nanobody-photosensitizer conjugates for photodynamic therapy in a pre-clinical model of head and neck cancer. J Control Release 2016; 229:93-105. [PMID: 26988602 PMCID: PMC7116242 DOI: 10.1016/j.jconrel.2016.03.014] [Citation(s) in RCA: 126] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2015] [Revised: 03/07/2016] [Accepted: 03/09/2016] [Indexed: 12/21/2022]
Abstract
Photodynamic therapy (PDT) induces cell death through local light activation of a photosensitizer (PS) and has been used to treat head and neck cancers. Yet, common PS lack tumor specificity, which leads to collateral damage to normal tissues. Targeted delivery of PS via antibodies has pre-clinically improved tumor selectivity. However, antibodies have long half-lives and relatively poor tissue penetration, which could limit therapeutic efficacy and lead to long photosensitivity. Here, in this feasibility study, we evaluate at the pre-clinical level a recently introduced format of targeted PDT, which employs nanobodies as targeting agents and a water-soluble PS (IRDye700DX) that is traceable through optical imaging. In vitro, the PS solely binds to cells and induces phototoxicity on cells overexpressing the epidermal growth factor receptor (EGFR), when conjugated to the EGFR targeted nanobodies. To investigate whether this new format of targeted PDT is capable of inducing selective tumor cell death in vivo, PDT was applied on an orthotopic mouse tumor model with illumination at 1h post-injection of the nanobody-PS conjugates, as selected from quantitative fluorescence spectroscopy measurements. In parallel, and as a reference, PDT was applied with an antibody-PS conjugate, with illumination performed 24h post-injection. Importantly, EGFR targeted nanobody-PS conjugates led to extensive tumor necrosis (approx. 90%) and almost no toxicity in healthy tissues, as observed through histology 24h after PDT. Overall, results show that these EGFR targeted nanobody-PS conjugates are selective and able to induce tumor cell death in vivo. Additional studies are now needed to assess the full potential of this approach to improving PDT.
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Affiliation(s)
- Pieter B A A van Driel
- Department of Radiology, Division of Molecular Imaging, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands; Percuros BV, Drienerlolaan 5, 7522 NB Enschede, The Netherlands
| | - Martin C Boonstra
- Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
| | - Maxime D Slooter
- Department of Radiology, Division of Molecular Imaging, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands; Percuros BV, Drienerlolaan 5, 7522 NB Enschede, The Netherlands
| | - Raimond Heukers
- Molecular Oncology, Cell Biology Division, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands
| | - Marieke A Stammes
- Department of Radiology, Division of Molecular Imaging, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands; Percuros BV, Drienerlolaan 5, 7522 NB Enschede, The Netherlands
| | - Thomas J A Snoeks
- Department of Radiology, Division of Molecular Imaging, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
| | - Henriette S de Bruijn
- Department of Otorhinolaryngology & Head and Neck Surgery, Center for Optical Diagnostics and Therapy, Erasmus Medical Center, s-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands
| | - Paul J van Diest
- Department of Pathology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
| | - Alexander L Vahrmeijer
- Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
| | - Paul M P van Bergen En Henegouwen
- Molecular Oncology, Cell Biology Division, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands
| | - Cornelis J H van de Velde
- Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
| | - Clemens W G M Löwik
- Department of Radiology, Division of Molecular Imaging, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
| | - Dominic J Robinson
- Department of Otorhinolaryngology & Head and Neck Surgery, Center for Optical Diagnostics and Therapy, Erasmus Medical Center, s-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands
| | - Sabrina Oliveira
- Molecular Oncology, Cell Biology Division, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.
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Nimotuzumab increases the anti-tumor effect of photodynamic therapy in an oral tumor model. Oncotarget 2016; 6:13487-505. [PMID: 25918252 PMCID: PMC4537029 DOI: 10.18632/oncotarget.3622] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2014] [Accepted: 04/08/2015] [Indexed: 12/23/2022] Open
Abstract
Oral squamous cell carcinoma (OSCC) represents 90% of all oral cancers and is characterized with poor prognosis and low survival rate. Epidermal growth factor receptor (EGFR) is highly expressed in oral cancer and is a target for cancer therapy and prevention. In this present work, we evaluate the efficacy of photodynamic therapy (PDT) in combination with an EGFR inhibitor, nimotuzumab in oral cancer cell lines and OSCC xenograft tumor model. PDT is a promising and minimally invasive treatment modality that involves the interaction of a photosensitizer, molecular oxygen and light to destroy tumors. We demonstrated that EGFR inhibitors nimotuzumab and cetuximab exhibits anti-angiogenic properties by inhibiting the migration and invasion of oral cancer cell lines and human endothelial cells. The EGFR inhibitors also significantly reduced tube formation of endothelial cells. Chlorin e6-PDT in combination with nimotuzumab and cetuximab reduced cell proliferation in different oral cancer and endothelial cells. Furthermore, our in vivo studies showed that the combination therapy of PDT and nimotuzumab synergistically delayed tumor growth when compared with control and PDT treated tumors. Downregulation of EGFR, Ki-67 and CD31 was observed in the tumors treated with combination therapy. Analysis of the liver and kidney function markers showed no treatment related toxicity. In conclusion, PDT outcome of oral cancer can be improved when combined with EGFR inhibitor nimotuzumab.
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Zhuang X, Ma X, Xue X, Jiang Q, Song L, Dai L, Zhang C, Jin S, Yang K, Ding B, Wang PC, Liang XJ. A Photosensitizer-Loaded DNA Origami Nanosystem for Photodynamic Therapy. ACS NANO 2016; 10:3486-95. [PMID: 26950644 PMCID: PMC4837698 DOI: 10.1021/acsnano.5b07671] [Citation(s) in RCA: 133] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/19/2023]
Abstract
Photodynamic therapy (PDT) offers an alternative for cancer treatment by using ultraviolet or visible light in the presence of a photosensitizer and molecular oxygen, which can produce highly reactive oxygen species that ultimately leading to the ablation of tumor cells by multifactorial mechanisms. However, this technique is limited by the penetration depth of incident light, the hypoxic environment of solid tumors, and the vulnerability of photobleaching reduces the efficiency of many imaging agents. In this work, we reported a cellular level dual-functional imaging and PDT nanosystem BMEPC-loaded DNA origami for photodynamic therapy with high efficiency and stable photoreactive property. The carbazole derivative BMEPC is a one- and two-photon imaging agent and photosensitizer with large two-photon absorption cross section, which can be fully excited by near-infrared light, and is also capable of destroying targets under anaerobic condition by generating reactive intermediates of Type I photodynamic reactions. However, the application of BMEPC was restricted by its poor solubility in aqueous environment and its aggregation caused quenching. We observed BMEPC-loaded DNA origami effectively reduced the photobleaching of BMEPC within cells. Upon binding to DNA origami, the intramolecular rotation of BMEPC became proper restricted, which intensify fluorescence emission and radicals production when being excited. After the BMEPC-loaded DNA origami are taken up by tumor cells, upon irradiation, BMEPC could generate free radicals and be released due to DNA photocleavage as well as the following partially degradation. Apoptosis was then induced by the generation of free radicals. This functional nanosystem provides an insight into the design of photosensitizer-loaded DNA origami for effective intracellular imaging and photodynamic therapy.
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Affiliation(s)
- Xiaoxi Zhuang
- Laboratory of Controllable Nanopharmaceuticals, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing 100190, China
| | - Xiaowei Ma
- Laboratory of Controllable Nanopharmaceuticals, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing 100190, China
- Corresponding Authors: .
| | - Xiangdong Xue
- Laboratory of Controllable Nanopharmaceuticals, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing 100190, China
| | - Qiao Jiang
- CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, National Center for Nanoscience and Technology, Beijing 100190, China
| | - Linlin Song
- CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, National Center for Nanoscience and Technology, Beijing 100190, China
| | - Luru Dai
- CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, National Center for Nanoscience and Technology, Beijing 100190, China
| | - Chunqiu Zhang
- Laboratory of Controllable Nanopharmaceuticals, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing 100190, China
| | - Shubin Jin
- Laboratory of Controllable Nanopharmaceuticals, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing 100190, China
| | - Keni Yang
- Laboratory of Controllable Nanopharmaceuticals, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing 100190, China
| | - Baoquan Ding
- CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, National Center for Nanoscience and Technology, Beijing 100190, China
| | - Paul C. Wang
- Fu Jen Catholic University, Taipei 24205, Taiwan
- Laboratory of Molecular Imaging, Department of Radiology, Howard University, Washington, DC 20060, United States
| | - Xing-Jie Liang
- Laboratory of Controllable Nanopharmaceuticals, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing 100190, China
- Corresponding Authors: .
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Calixto GMF, Bernegossi J, de Freitas LM, Fontana CR, Chorilli M. Nanotechnology-Based Drug Delivery Systems for Photodynamic Therapy of Cancer: A Review. Molecules 2016; 21:342. [PMID: 26978341 PMCID: PMC6274468 DOI: 10.3390/molecules21030342] [Citation(s) in RCA: 327] [Impact Index Per Article: 36.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2015] [Revised: 03/04/2016] [Accepted: 03/07/2016] [Indexed: 01/10/2023] Open
Abstract
Photodynamic therapy (PDT) is a promising alternative approach for improved cancer treatment. In PDT, a photosensitizer (PS) is administered that can be activated by light of a specific wavelength, which causes selective damage to the tumor and its surrounding vasculature. The success of PDT is limited by the difficulty in administering photosensitizers (PSs) with low water solubility, which compromises the clinical use of several molecules. Incorporation of PSs in nanostructured drug delivery systems, such as polymeric nanoparticles (PNPs), solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), gold nanoparticles (AuNPs), hydrogels, liposomes, liquid crystals, dendrimers, and cyclodextrin is a potential strategy to overcome this difficulty. Additionally, nanotechnology-based drug delivery systems may improve the transcytosis of a PS across epithelial and endothelial barriers and afford the simultaneous co-delivery of two or more drugs. Based on this, the application of nanotechnology in medicine may offer numerous exciting possibilities in cancer treatment and improve the efficacy of available therapeutics. Therefore, the aim of this paper is to review nanotechnology-based drug delivery systems for photodynamic therapy of cancer.
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Affiliation(s)
- Giovana Maria Fioramonti Calixto
- Faculdade de Ciências Farmacêuticas, UNESP-Univ. Estadual Paulista, Campus Araraquara, Departamento de Fármacos e Medicamentos, Araraquara 14800-903 SP, Brazil.
| | - Jéssica Bernegossi
- Faculdade de Ciências Farmacêuticas, UNESP-Univ. Estadual Paulista, Campus Araraquara, Departamento de Fármacos e Medicamentos, Araraquara 14800-903 SP, Brazil.
| | - Laura Marise de Freitas
- Faculdade de Ciências Farmacêuticas, UNESP-Univ. Estadual Paulista, Campus Araraquara, Departamento de Análises Clínicas, Araraquara 14800-903 SP, Brazil.
| | - Carla Raquel Fontana
- Faculdade de Ciências Farmacêuticas, UNESP-Univ. Estadual Paulista, Campus Araraquara, Departamento de Análises Clínicas, Araraquara 14800-903 SP, Brazil.
| | - Marlus Chorilli
- Faculdade de Ciências Farmacêuticas, UNESP-Univ. Estadual Paulista, Campus Araraquara, Departamento de Fármacos e Medicamentos, Araraquara 14800-903 SP, Brazil.
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Li S, Chang K, Sun K, Tang Y, Cui N, Wang Y, Qin W, Xu H, Wu C. Amplified Singlet Oxygen Generation in Semiconductor Polymer Dots for Photodynamic Cancer Therapy. ACS APPLIED MATERIALS & INTERFACES 2016; 8:3624-3634. [PMID: 26492203 DOI: 10.1021/acsami.5b07995] [Citation(s) in RCA: 100] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/05/2023]
Abstract
This paper described the energy-transfer amplified singlet oxygen generation in semiconductor polymer dots (Pdots) for in vitro and in vivo photodynamic therapy. Hydrophobic photosensitizer tetraphenylporphyrin was facilely doped in the nanoparticles consisting of densely packed semiconductor polymers. Optical characterizations indicated that the fluorescence of Pdots was completely quenched by the photosensitizer, yielding an energy transfer efficiency of nearly 100% and singlet-oxygen generation quantum yield of ∼50%. We evaluated the cellular uptake, dark toxicity, and photodynamic therapy of the Pdot photosensizer in human gastric adenocarcinoma cells. The in vitro studies indicated that cancer cells were efficiently destroyed at very low dose of the Pdots such as 1 μg/mL by using the light dose of 90 J/cm(2), which is considerably less than that in clinical practice. The antitumor effect of the Pdots was further evaluated in vivo with human gastric adenocarcinoma xenografts in Balb/c nude mice, which show that the xenograft tumors were significantly inhibited and eradicated in some cases. Our results indicate the energy transfer amplified Pdot platforms have great therapeutic potential for treating malignant cancers.
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Affiliation(s)
- Shouying Li
- Department of Gastroenterology, The First Hospital of Jilin University , Changchun 130021, China
| | | | | | - Ying Tang
- Department of Gastroenterology, The First Hospital of Jilin University , Changchun 130021, China
| | | | | | | | - Hong Xu
- Department of Gastroenterology, The First Hospital of Jilin University , Changchun 130021, China
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Moghissi K, Dixon K, Gibbins S. A Surgical View of Photodynamic Therapy in Oncology: A Review. Surg J (N Y) 2015; 1:e1-e15. [PMID: 28824964 PMCID: PMC5530619 DOI: 10.1055/s-0035-1565246] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2015] [Accepted: 08/25/2015] [Indexed: 12/18/2022] Open
Abstract
Clinical photodynamic therapy (PDT) has existed for over 30 years, and its scientific basis has been known and investigated for well over 100 years. The scientific foundation of PDT is solid and its application to cancer treatment for many common neoplastic lesions has been the subject of a huge number of clinical trials and observational studies. Yet its acceptance by many clinicians has suffered from its absence from the undergraduate and/or postgraduate education curricula of surgeons, physicians, and oncologists. Surgeons in a variety of specialties many with years of experience who are familiar with PDT bear witness in many thousands of publications to its safety and efficacy as well as to the unique role that it can play in the treatment of cancer with its targeting precision, its lack of collateral damage to healthy structures surrounding the treated lesions, and its usage within minimal access therapy. PDT is closely related to the fluorescence phenomenon used in photodiagnosis. This review aspires both to inform and to present the clinical aspect of PDT as seen by a surgeon.
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Affiliation(s)
- K. Moghissi
- The Yorkshire Laser Centre, Goole and District Hospital, Goole, East Yorkshire, United Kingdom
| | - Kate Dixon
- The Yorkshire Laser Centre, Goole and District Hospital, Goole, East Yorkshire, United Kingdom
| | - Sally Gibbins
- The Yorkshire Laser Centre, Goole and District Hospital, Goole, East Yorkshire, United Kingdom
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Affiliation(s)
- Sasidharan Swarnalatha Lucky
- NUS Graduate School for Integrative Sciences & Engineering (NGS), National University of Singapore, Singapore, Singapore 117456
- Department
of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore, Singapore 117576
| | - Khee Chee Soo
- Division
of Medical Sciences, National Cancer Centre Singapore, Singapore, Singapore 169610
| | - Yong Zhang
- NUS Graduate School for Integrative Sciences & Engineering (NGS), National University of Singapore, Singapore, Singapore 117456
- Department
of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore, Singapore 117576
- College
of Chemistry and Life Sciences, Zhejiang Normal University, Zhejiang, P. R. China 321004
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Abstract
Photodynamic therapy (PDT) is a light-based intervention with a long and successful clinical track record for both oncology and non-malignancies. In cancer patients, a photosensitizing agent is intravenously, orally or topically applied and allowed time to preferentially accumulate in the tumor region. Light of the appropriate wavelength and intensity to activate the particular photosensitizer employed is then introduced to the tumor bed. The light energy will activate the photosensitizer, which in the presence of oxygen should allow for creation of the toxic photodynamic reaction generating reactive oxygen species. The photodynamic reaction creates a cascading series of events including initiation of apoptotic and necrotic pathways both in tumor and neovasculature, leading to permanent lesion destruction often with upregulation of the immune system. Cutaneous phototoxicity from unintentional sunlight exposure remains the most common morbidity from PDT. This paper will highlight current research and outcomes from the basic science and clinical applications of oncologic PDT and interpret how these findings may lead to enhanced and refined future PDT.
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Affiliation(s)
- Ron R Allison
- 21st Century Oncology, 801 WH Smith Boulevard, Greenville, NC 27834, USA.
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Trinidad AJ, Hong SJ, Peng Q, Madsen SJ, Hirschberg H. Combined concurrent photodynamic and gold nanoshell loaded macrophage-mediated photothermal therapies: an in vitro study on squamous cell head and neck carcinoma. Lasers Surg Med 2014; 46:310-8. [PMID: 24648368 DOI: 10.1002/lsm.22235] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/03/2014] [Indexed: 11/10/2022]
Abstract
BACKGROUND AND OBJECTIVE Treatment modalities, such as hyperthermia and photodynamic therapy (PDT) have been used in the treatment of a variety of head and neck squamous cell carcinoma (HNSCC), either alone or as an adjuvant therapy. Macrophages loaded with gold nanoshells, which convert near-infrared light to heat, can be used as transport vectors for photothermal hyperthermia of tumors. The purpose of this study was to investigate the effects of combined macrophage mediated photothermal therapy (PTT) and PDT on HNSCC cells. STUDY DESIGN/MATERIALS AND METHODS Gold nanoshell loaded rat macrophages either alone or combined with human FaDu squamous cells in hybrid monolayers were subjected to PTT, PDT, or a simultaneous combination of the two light treatments. Therapies were given concurrently employing two laser light sources of λ = 670 nm (PDT) and λ = 810 nm (PTT), respectively. RESULTS Significant uptake of gold nanospheres (AuNS) by rat alveolar macrophages was observed thus providing the rationale for their use as delivery vectors. Viability of the AuNS-loaded Ma was reduced to 35 and 12% of control values at an irradiance of 14 or 28 W/cm(2) administered over a 5 minute period respectively. No significant cytotoxicity was observed for empty Ma for similar PTT exposure. AlPcS2a mediated PDT at a fluence level of 0.25 J/cm(2) and PTT at 14 W/cm(2) irradiance had little effect on cell viability for the FaDu/Ma (ratio 2:1) hybrid monolayers. In contrast, combined treatment reduced the cell viability to less than 40% at these same laser power settings. CONCLUSIONS The results of this study provide proof of concept for the use of macrophages as a delivery vector of AuNS for photothermal enhancement of the effects of PDT on squamous cell carcinoma. A significant synergy was demonstrated with combined PDT and PTT compared to each modality applied separately.
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Affiliation(s)
- Anthony J Trinidad
- Beckman Laser Institute and Medical Clinic, University of California, Irvine, California, 92612
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Mesoscopic fluorescence tomography of a photosensitizer (HPPH) 3D biodistribution in skin cancer. Acad Radiol 2014; 21:271-80. [PMID: 24439340 DOI: 10.1016/j.acra.2013.11.009] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2013] [Revised: 11/09/2013] [Accepted: 11/11/2013] [Indexed: 01/15/2023]
Abstract
RATIONALE AND OBJECTIVES Photodynamic therapy (PDT) is a promising strategy for treating cancer. PDT involves three components: a photosensitizer (PS) drug, a specific wavelength of drug-activating light, and oxygen. A challenge in PDT is the unknown biodistribution of the PS in the target tissue. In this preliminary study, we report the development of a new approach to image in three dimensions the PS biodistribution in a noninvasive and fast manner. MATERIALS AND METHODS A mesoscopic fluorescence tomography imaging platform was used to image noninvasively the biodistribution of 2-[1-hexyloxyethyl]-2 devinyl pyropheophorbide-a (HPPH) in preclinical skin cancer models. Seven tumors were imaged and optical reconstructions were compared to nonconcurrent ultrasound data. RESULTS Successful imaging of the HPPH biodistribution was achieved on seven skin cancer tumors in preclinical models with a typical acquisition time of 1 minute. Two-dimensional fluorescence signals and estimated three-dimensional PS distributions were located within the lesions. However, HPPH distribution was highly heterogeneous with the tumors. Moreover, HPPH distribution volume and tumor volume as estimated by ultrasound did not match. CONCLUSIONS The results of this proof-of-concept study demonstrate the potential of MFMT to image rapidly the HPPH three-dimensional biodistribution in skin cancers. In addition, these preliminary data indicate that the PS biodistribution in skin cancer tumors is heterogeneous and does not match anatomical data. Mesoscopic fluorescence molecular tomography, by imaging fluorescence signals over large areas with high spatial sampling and at fast acquisition speeds, may be a new imaging modality of choice for planning and optimizing of PDT treatment.
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Yu CH, Yu CC. Photodynamic therapy with 5-aminolevulinic acid (ALA) impairs tumor initiating and chemo-resistance property in head and neck cancer-derived cancer stem cells. PLoS One 2014; 9:e87129. [PMID: 24475244 PMCID: PMC3901774 DOI: 10.1371/journal.pone.0087129] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2013] [Accepted: 12/22/2013] [Indexed: 12/18/2022] Open
Abstract
Background Head and neck cancer (HNC) ranks the fourth leading malignancy and cancer death in male population in Taiwan. Despite recent therapeutic advances, the prognosis for HNC patients is still dismal. New strategies are urgently needed to improve the chemosensitization to conventional chemotherapeutic drugs and clinical responses of HNC patients. Studies have demonstrated that topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) is being used in the treatment of various human premalignant and malignant lesions with some encouraging clinical outcomes. However, the molecular mechanisms of ALA-PDT in the therapeutic effect in HNC tumorigenesis and whether ALA-PDT as chemosensitizer for HNC treatment remain unclear. Accumulating data support cancer stem cells (CSCs) contributes chemo-resistance in HNC. Based on the previous studies, the purpose of the study is to investigate the effect of ALA-PDT on CSCs and chemosensitization property in HNC. Methodology/Principal Finding CSCs marker ALDH1 activity of HNC cells with ALA-PDT treatment as assessed by the Aldefluor assay flow cytometry analysis. Secondary Sphere-forming self-renewal, stemness markers expression, and invasiveness of HNC-CSCs with ALA-PDT treatment were presented. We observed that the treatment of ALA-PDT significantly down-regulated the ALDH1 activity and CD44 positivity of HNC-CSCs. Moreover, ALA-PDT reduced self-renewal property and stemness signatures expression (Oct4 and Nanog) in sphere-forming HNC-CSCs. ALA-PDT sensitized highly tumorigenic HNC-CSCs to conventional chemotherapies. Lastly, synergistic effect of ALA-PDT and Cisplatin treatment attenuated invasiveness/colongenicity property in HNC-CSCs. Conclusion/Significance Our results provide insights into the clinical prospect of ALA-PDT as a potential chemo-adjuvant therapy against head and neck cancer through eliminating CSCs property.
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MESH Headings
- Aldehyde Dehydrogenase 1 Family
- Aminolevulinic Acid/pharmacology
- Biomarkers, Tumor/genetics
- Biomarkers, Tumor/metabolism
- Cell Line, Tumor
- Cell Transformation, Neoplastic/drug effects
- Cell Transformation, Neoplastic/genetics
- Cell Transformation, Neoplastic/metabolism
- Cell Transformation, Neoplastic/pathology
- Cisplatin/pharmacology
- Drug Resistance, Neoplasm/drug effects
- Drug Resistance, Neoplasm/genetics
- Drug Synergism
- Gene Expression Regulation, Neoplastic
- Head and Neck Neoplasms/drug therapy
- Head and Neck Neoplasms/genetics
- Head and Neck Neoplasms/metabolism
- Head and Neck Neoplasms/pathology
- Homeodomain Proteins/genetics
- Homeodomain Proteins/metabolism
- Humans
- Hyaluronan Receptors/genetics
- Hyaluronan Receptors/metabolism
- Isoenzymes/antagonists & inhibitors
- Isoenzymes/genetics
- Isoenzymes/metabolism
- Nanog Homeobox Protein
- Neoplastic Stem Cells/drug effects
- Neoplastic Stem Cells/metabolism
- Neoplastic Stem Cells/pathology
- Octamer Transcription Factor-3/genetics
- Octamer Transcription Factor-3/metabolism
- Photochemotherapy
- Photosensitizing Agents/pharmacology
- Primary Cell Culture
- Radiation-Sensitizing Agents/pharmacology
- Retinal Dehydrogenase/antagonists & inhibitors
- Retinal Dehydrogenase/genetics
- Retinal Dehydrogenase/metabolism
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Affiliation(s)
- Chuan-Hang Yu
- School of Dentistry, Chung Shan Medical University, Taichung, Taiwan
- Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan
- * E-mail: (C-HY); (C-CY)
| | - Cheng-Chia Yu
- School of Dentistry, Chung Shan Medical University, Taichung, Taiwan
- Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan
- Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan
- * E-mail: (C-HY); (C-CY)
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Sunar U. Monitoring photodynamic therapy of head and neck malignancies with optical spectroscopies. World J Clin Cases 2013; 1:96-105. [PMID: 24303476 PMCID: PMC3845916 DOI: 10.12998/wjcc.v1.i3.96] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2013] [Revised: 04/02/2013] [Accepted: 05/08/2013] [Indexed: 02/05/2023] Open
Abstract
In recent years there has been significant developments in photosensitizers (PSs), light sources and light delivery systems that have allowed decreasing the treatment time and skin phototoxicity resulting in more frequent use of photodynamic therapy (PDT) in the clinical settings. Compared to standard treatment approaches such as chemo-radiation and surgery, PDT has much reduced morbidity for head and neck malignancies and is becoming an alternative treatment option. It can be used as an adjunct therapy to other treatment modalities without any additive cumulative side effects. Surface illumination can be an option for pre-malignant and early-stage malignancies while interstitial treatment is for debulking of thick tumors in the head and neck region. PDT can achieve equivalent or greater efficacy in treating head and neck malignancies, suggesting that it may be considered as a first line therapy in the future. Despite progressive development, clinical PDT needs improvement in several topics for wider acceptance including standardization of protocols that involve the same administrated light and PS doses and establishing quantitative tools for PDT dosimetry planning and response monitoring. Quantitative measures such as optical parameters, PS concentration, tissue oxygenation and blood flow are essential for accurate PDT dosimetry as well as PDT response monitoring and assessing therapy outcome. Unlike conventional imaging modalities like magnetic resonance imaging, novel optical imaging techniques can quantify PDT-related parameters without any contrast agent administration and enable real-time assessment during PDT for providing fast feedback to clinicians. Ongoing developments in optical imaging offer the promise of optimization of PDT protocols with improved outcomes.
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