Sonodynamic therapy (SDT) shows substantial potentials in cancer treatment thanks to the deep tissue penetration of ultrasound. However, its clinical translation suffers from the potential damages to healthy tissues and the resistance of tumors, particularly from cancer stem-like cells (CSCs), to the ultrasound. To address these challenges, we designed a novel glutathione (GSH)-activated nanomedicine to simultaneously enhance the safety and efficacy of SDT by in situ regulating the generation of reactive oxygen species (ROS) and copper metabolism. This nanomedicine, Es@CuTCPP, was created by loading elesclomol (Es) onto CuTCPP nanosheets. By accumulating this nanomedicine in tumors, the Cu(II)-TCPP is reduced to the highly sonosensitive Cu(I)-TCPP by the intra-tumoral-overexpressed GSH, leading to the production of abundant ROS upon ultrasound exposure, which effectively kills large amounts of tumor cells. Concurrently, the released copper ions react with co-released Es to form a CuEs complex, which induces cuproptosis of CSCs surviving the ROS attack by disrupting cellular copper metabolism, evidently amplifying the effectiveness of SDT. This work presents the first paradigm of a GSH-activated and cuproptosis-enhanced SDT approach, offering a promising novel strategy for cancer therapy.

Recent advancements in multifunctional nanomaterials for cancer therapy have highlighted porphyrin-based metal-organic frameworks (MOFs) as promising candidates due to their unique properties and versatile applications. This overview focuses on the use of porphyrin-based MOFs for combined photodynamic therapy (PDT) and photothermal therapy (PTT) in cancer treatment. Porphyrin-based MOFs offer high porosity, tuneable structures, and excellent stability, making them ideal for drug delivery and therapeutic applications. The incorporation of porphyrin molecules into the MOF framework enhances light absorption and energy transfer, leading to improved photodynamic and photothermal effects. Additionally, the porosity of MOFs allows for the encapsulation of therapeutic agents, further enhancing efficacy. In PDT, porphyrin-based MOFs generate reactive oxygen species (ROS) upon light activation, destroying cancer cells. The photothermal properties enable the conversion of light energy into heat, resulting in localised hyperthermia and tumour ablation. The combination of PDT and PTT in a single platform offers synergistic effects, leading to better therapeutic outcomes, reduced side effects, and improved selectivity. This dual-modal treatment strategy provides precise spatiotemporal control over the treatment process, paving the way for next-generation therapeutics with enhanced efficacy and reduced side effects. Further research and optimisation are needed for clinical applications.

The rapid development of nanotechnology has significantly advanced the application of nanophotocatalysis in the medical field, particularly for cancer therapy. Traditional cancer treatments, such as chemotherapy and radiotherapy, often cause severe side effects, including damage to healthy tissues and the development of drug resistance. In contrast, nanophotocatalytic therapy offers a promising approach by utilizing nanomaterials that generate reactive oxygen species (ROS) under light activation, allowing for precise tumor targeting and minimizing collateral damage to surrounding tissues. This review systematically explores the latest advancements in highly efficient nanophotocatalysts for cancer treatment, focusing on their toxicological profiles, underlying mechanisms for cancer cell eradication, and potential for clinical application. Recent research shows that nanophotocatalysts, such as TiO2, In2O3, and g-C3N4 composites, along with photocatalysts with high conduction band or high valence band positions, generate ROS under light irradiation, which induces oxidative stress and leads to cancer cell apoptosis or necrosis. These ROS cause cellular damage by interacting with key biological molecules such as DNA, proteins, and lipids, triggering a cascade of biochemical reactions that ultimately result in cancer cell death. Furthermore, strategies such as S-scheme heterojunctions and oxygen vacancies (OVs) have been incorporated to enhance charge separation efficiency and light absorption, resulting in increased ROS generation, which improves photocatalytic performance for cancer cell targeting. Notably, these photocatalysts exhibit low toxicity to healthy cells, making them a safe and effective treatment modality. The review also discusses the challenges associated with photocatalytic cancer therapy, including limitations in light penetration and the need for improved biocompatibility. The findings suggest that nanophotocatalytic technology holds significant potential for precision cancer therapy, paving the way for safer and more effective treatment strategies.

Cyanide is highly toxic, with widespread industrial use posing serious environmental risks. Effective materials for detecting and filtering cyanide from water are urgently needed. This study introduces a novel approach utilizing Cu-TCPP (TCPP = o-tetra(4-carboxyphenyl)porphine) metal-organic nanosheets (MONS) embedded in thin-film composite membranes, offering a multifunctional solution for cyanide detection and filtration. Ultrathin Cu-TCPP MONs were synthesized using a surfactant-assisted method featuring highly accessible metal centers that enhance cyanide interaction and detection. The membranes, developed by modifying cellulose acetate (CA) with Cu-TCPP MONs, demonstrated exceptional performance for cyanide removal. The 6% Cu-TCPP/CA membrane exhibited a 2.3-fold increase in pure water permeability and achieved a cyanide removal efficiency of 94.68%, significantly outperforming the pristine 0% Cu-TCPP/CA membrane (Pure Water Permeability (PWP) = 380.83 L m-2 h-1 bar-1; CN- removal = 5.01%). This is the first report describing the detection and removal of CN- in water using the membrane technique in literature. In addition to its removal efficiency, the Cu-TCPP MONs showed remarkable detection capabilities, with a calculated limit of detection of 1.76 × 10-7 M, surpassing World Health Organization (WHO) and United States Environmental Protection Agency (EPA) safety standards for cyanide levels in water. Additionally, Cu-TCPP MONs, a bioimaging agent with excellent cell viability, were deployed to detect CN- in MiaPaCa-2 cells, detecting concentrations as low as 0.1 ppm.

In this study, we developed a multifunctional nanoplatform to address the limitations of strictly acidic pH for the Fenton reaction involving Fe3O4 and the low efficiency of mono treatments. The hybrid material, Fe3O4@Cu-TCPP, was assembled through hydrophobic interactions of polyvinylpyrrolidone (PVP) coated on its surface. The efficiency of the Fenton reaction using Fe3O4 was significantly enhanced by the photo-Fenton process in the presence of Cu-TCPP. The generation of hydroxyl radicals by Fe3O4@Cu-TCPP was markedly increased under laser irradiation (λ = 660 nm) in solution. Fe3O4@Cu-TCPP demonstrated a robust ability to produce reactive oxygen species through chemodynamic and photodynamic processes independent of that of O2. In vivo experimental results indicated that Fe3O4@Cu-TCPP facilitated T2-weighted magnetic resonance imaging-mediated synergistic chemodynamic and photodynamic therapies in a 4T1 mouse model.

High locoregional recurrence rates and potential wound infections remain a significant challenge for postoperative breast cancer patients. Herein, we developed a dual-network hyaluronic acid (HA) nanocomposite hydrogel composed of herring sperm DNA (hsDNA) bridged methacrylated HA (HAMA) and FeMg-LDH-ppsa nanohybrid chelated catechol-modified HA (HADA) for the prevention of breast cancer recurrent, anti-infection, and promoting wound healing. Dynamic reversible hsDNA cross-linking combined with metal-catechol chelating renders the hydrogel injectability, rapid self-healing ability, and enhanced mechanical properties. FeMg-LDH-ppsa nanohybrids obtained by in situ polymerization of aniline derivatives in the FeMg-LDH interlayer exhibited excellent photothermal effect. Upon near-infrared (NIR) irradiation, the photothermal effect mediated by FeMg-LDH-ppsa can unwind the hsDNA duplex, enabling the controlled release of preloaded DOX for synergistic photothermal-chemotherapy antitumor. Meanwhile, the catechol-metal (Fe3+/Mg2+) moieties in the hydrogel enhanced tissue adhesion and exhibited intrinsic antimicrobial and bioactive properties, which in combination with the NIR-assisted photothermal effect, significantly accelerated infected wound healing through sterilizing microorganisms, alleviating inflammation, re-epithelialization, and angiogenesis. Overall, this multifunctional hydrogel represented a promising candidate in postoperative wound management for simultaneous tumor elimination, antiinfection, and wound repair.

Photodynamic therapy (PDT) utilizing metal-organic frameworks (MOFs) has developed as a new and efficacious treatment for malignant tumors located on the surface of the human body. In order to achieve more effective PDT treatment outcomes, the traditional method has been to increase the intensity of the laser irradiation, but this approach can easily lead to tissue burns. In this study, we developed a new type of nanoparticle, F68-PKI@PCN224, aims to achieve effective PDT upon medullary thyroid carcinoma (MTC) which is an uncommon form of thyroid cancer that originates in the parafollicular cells of the thyroid and the therapeutic outlook for patients with MTC remains unsatisfactory. F68-PKI@PCN224 combines the antitumor features of PDT with mammalian target of rapamycin (mTOR) inhibitor PKI-587 (PKI). The tumor sensitization, slow release, and pH response features of F68-PKI@PCN224 was demonstrated by a series of in vitro and in vivo experiments / assays. F68-PKI@PCN224 achieved the long-term activation and slow releasing of PKI and TCPP in MTC tumor tissues. During the process of generating PDT effects, F68-PKI@PCN224 enhanced the tumor's sensitivity to PDT, direct laser irradiation of MTC cells or subcutaneous tumor tissues. As a result, low-dose phototherapy achieves a higher anti-tumor effect upon F68-PKI@PCN224 compared with TCPP. This study reveals the synergistic effect between tumor sensitization by mTOR inhibitor and PDT and initially unveils the mechanism of action of these nanoparticles.

Chemotherapy is a widely used cancer treatment, however, it can have notable side effects owing to the high-doses of drugs administered. Sonodynamic therapy (SDT) induced by sonosensitizers has emerged as a promising approach to treat cancer, however, there is limited research evaluating its therapeutic effects on human tumors. In this study, we introduced a dual therapy that combines low-dose chemotherapeutic drugs with enhanced sonodynamic therapy, utilizing barium titanate (BaTiO3, BTO) nanoparticles (NPs) as sonosensitizers to treat tumor organoids. We demonstrated that ultrasound could improve the cellular uptake of chemotherapy drugs, while the chemotherapeutic effect of the drugs made it easier for BTO NPs to enter tumor cells, and the dual therapy synergistically inhibited tumor cell viability. Moreover, different patient-derived tumor organoids exhibited different sensitivities to this therapy, highlighting the potential to evaluate individual responses to combination therapies prior to clinical intervention. Furthermore, this dual therapy exhibited therapeutic effects equivalent to those of high-dose chemotherapy drugs on drug-resistant tumor organoids and showed the potential to enhance the efficacy of killing drug-resistant tumors. In addition, the biosafety of the BTO NPs was successfully verified in live mice via oral administration. This evidence confirms the reliable and safe nature of the dual therapy approach, making it a feasible option for precise and personalized therapy in clinical applications.

Myocardial infarction (MI) is a serious cardiovascular disease that often results in a significant decline in heart function and associated complications. α-SMA (α-smooth muscle cell actin) is an important biomarker in the process of cardiac remodeling and repair, and its expression level is closely related to myocardial remodeling and prognosis. Therefore, the purpose of this study was to investigate the potential of nanoparticles containing cardiomyocyte targeting peptides in predicting prognosis and α-SMA protein expression after myocardial infarction, with a view to providing new therapeutic strategies and clinical guidelines. In this study, a novel targeting nanoparticle was constructed, using cardiomyocyte specific peptides as targeting ligands, and characterized by loading different drugs. Subsequently, a mouse model of myocardial infarction was used to systematically evaluate the effect of nanoparticles on α-SMA protein expression and prognosis prediction ability after MI. The expression level of α-SMA was analyzed by Western blot and immunohistochemistry, and the prognosis was evaluated by cardiac function assessment. The study found that nanoparticles containing cardiomyocyte targeting peptides significantly increased α-SMA expression levels and improved heart function in animal models of myocardial infarction. Compared with the control group, the application of targeted nanoparticles was closely related to the level of myocardial cell repair and fibrosis, and could effectively predict the prognosis after myocardial infarction. Therefore, nanoparticles containing cardiomyocyte targeting peptides can not only effectively improve the expression of α-SMA, but also serve as an important prognostic tool after myocardial infarction.

Metal-organic frameworks (MOFs) offer innovative solutions to the limitations of traditional oral drug delivery systems through their unique combination of metal ions and organic ligands. This review systematically examines the structural properties and principles of MOFs, setting the stage for their application in drug delivery. It discusses various classes of MOFs, including those based on zirconium, iron, zinc, copper, titanium, aluminum, potassium, and magnesium, assessing their drug-loading capacities, biocompatibility, and controlled release mechanisms. The effectiveness of MOFs is illustrated through case studies that highlight their capabilities in enhancing drug solubility, providing protection against the harsh gastrointestinal environment, and enabling precise drug release. The review addresses potential challenges, particularly the toxicity concerns associated with MOFs, and calls for further research into their biocompatibility and interactions with biological systems. It concludes by emphasizing the potential of MOFs in revolutionizing oral drug delivery, highlighting the critical need for comprehensive research to harness their full potential in clinical applications.

As the third essential trace element in the human body, copper plays a crucial role in various physiological processes, which lays the foundation for its broad applications in cancer treatments. The overview of copper, including pharmacokinetics, signaling pathways, and homeostasis dysregulation, is hereby discussed. Additionally, cuproptosis, as a newly proposed cell death mechanism associated with copper accumulation, is analyzed and further developed for efficient cancer treatment. Different forms of Cu-based nanoparticles and their advantages, as well as limiting factors, are introduced. Moreover, the unique characteristics of Cu-based nanoparticles give rise to their applications in various imaging modalities. In addition, Cu-based nanomaterials are featured by their excellent photothermal property and ROS-associated tumor-killing potential, which are widely explored in diverse cancer therapies and combined therapies. Reducing the concentration of Cu2+/Cu+ is another cancer-killing method, and chelators can meet this need. More importantly, challenges and future prospects are identified for further research.

Photodynamic therapy (PDT) has attracted increasing attention in the clinical treatment of epidermal and luminal tumors. However, the PDT efficacy in practice is severely impeded by tumor hypoxia and the adverse factors associated with hydrophobic photosensitizers (PSs), including low delivery capacity, poor photoactivity and limited ROS diffusion. In this study, Pt nanozymes decorated two-dimensional (2D) porphyrin metal-organic framework (MOF) nanosheets (PMOF@HA) were fabricated and investigated to conquer the obstacles of PDT against hypoxic tumors.

PMOF@HA was synthesized by the coordination of transition metal iron (Zr4+) and PS (TCPP), in situ generation of Pt nanozyme and surface modification with hyaluronic acid (HA). The abilities of hypoxic relief and ROS generation were evaluated by detecting the changes of O2 and 1O2 concentration. The cellular uptake was investigated using flow cytometry and confocal laser scanning microscopy. The SMMC-7721 cells and the subcutaneous tumor-bearing mice were used to demonstrate the PDT efficacy of PMOF@HA in vitro and in vivo, respectively.

Benefiting from the 2D structure and inherent properties of MOF materials, the prepared PMOF@HA could not only serve as nano-PS with high PS loading but also ensure the rational distance between PS molecules to avoid aggregation-induced quenching, enhance the photosensitive activity and promote the rapid diffusion of generated radical oxide species (ROS). Meanwhile, Pt nanozymes with catalase-like activity effectively catalyzed intratumoral overproduced H2O2 into O2 to alleviate tumor hypoxia. Additionally, PMOF@HA, with the help of externally coated HA, significantly improved the stability and increased the cell uptake by CD44 overexpressed tumor cells to strengthen O2 self-supply and PDT efficacy.

This study provided a new strategy of integrating 2D porphyrin MOF nanosheets with nanozymes to conquer the obstacles of PDT against hypoxic tumors.

With large specific surface area, controllable pore size, increased active sites, and structural stability, two-dimensional metal organic frameworks (2D MOFs) have emerged as promising nanomedicines in cancer therapy. These distinctive features make 2D MOFs particularly advantageous in cancer treatment and the corresponding application has gained considerable popularity, signifying significant application potential. Herein, recent advances in various applications including drug delivery and chemotherapy, photodynamic therapy, sonodynamic therapy, chemodynamic therapy, catalytic therapy, and combined therapy were summarized, with emphasis on the latest progress of new materials and mechanisms for these processes. Moreover, the current challenges, potential solutions, and possible future directions are discussed as well.

Solar-driven upgrading of biomass-derived 5-hydroxylmethylfurfural (HMF) to 2,5-furandicarboxylic acid (FDCA) holds great promise for sustainable production of bio-plastics and resins. However, the process is limited by poor selectivity and sluggish kinetics due to the vertical coordination of HMF at relatively strong metal sites. Here, we purposely developed a Cu(II) porphyrin framework featuring side-chain incorporated urea linkages, denoted as TBUPP-Cu MOF, to render HMF a weak hydrogen bond at the urea site and flat adsorption via π-π stacking with the benzene moiety. The unique configuration promotes the approaching of -CHO of HMF to the photoexcited porphyrin ring towards kinetically and thermodynamically favourable intermediate formation and subsequent desorption. The charge localisation and orbital energy alignment enable the selective activation of O2 over the porphyrin to generate ⋅O2 - and 1O2 instead of highly oxidative H2O2 and ⋅OH via spin-flip electron transfer, which drive the ambient oxidation of proximal -CHO. The effective utilisation of redox species and circumvented over-oxidation facilitate a FDCA selectivity of >90 % with a high turnover number of 193 molHMF molCu -1. The facile purification of high-purity FDCA and zero-waste recycling of intermediates and durable catalyst feature TBUPP-Cu MOF a promising photo-oxidation platform towards net-zero biorefining and organic transformations.

Pyroptosis is regarded as a promising strategy to modulate tumor immune microenvironments for anticancer therapy. Although pyroptosis inducers have been extensively explored in the biomedical field, their drug resistance, off-targeting capacity, and adverse effects do not fulfill the growing demands of therapy. Nowadays, metal-organic frameworks (MOFs) with unique structures and facile synthesis/functionalization characteristics have shown great potential in anticancer therapy. The flexible choices of metal ions and ligands endow MOFs with inherent anti-cancer efficiency, whereas the porous structures in MOFs make them ideal vehicles for delivering various chemodrug-based pyroptosis inducers. In this review, we provide the latest advances in MOF-based materials to evoke pyroptosis and give a brief but comprehensive review of the different types of MOFs for pyroptosis-mediated cancer therapy. Finally, we also discuss the current challenges of MOF-based pyroptosis inducers and their future prospects in this field.

Multifunctional nanomaterials with potential applications in both bioimaging and photodynamic-sonodynamic therapy have great advantages in cancer theranostic, but the design and preparation of "all-in-one" type of multifunctional nanomaterials with single component remains challenging. Herein the "all-in-one" type of Mn-PpIX (Protoporphyrin IX) coordination polymers (MnPPs) was reported as efficient nano-photo/sonosensitizers. The MnPPs had an average size of ∼ 110 nm. Upon light/US (ultrasound) irradiation for 5 min, 61.8 % (light) and 32.4 % (US) of DPBF (1.3-diphenyl isobenzofuran) was found to be oxidized by MnPPs, which showed effective ROS (reactive oxygen species) generation for photodynamic/sonodynamic therapy (PDT/SDT). In addition, MnPPs revealed excellent biosafety and could be engulfed by cells to produce intracellular ROS under light/US excitation for efficient killing tumor cells. When MnPPs was injected into mice, the tumor could be monitored via MRI (magnetic resonance imaging). In addition, tumor growth could be significantly inhibited by the synergistic PDT-SDT. Therefore, the present study not only represents MnPPs as an "all-in-one" type of multifunctional nanomaterials for MRI-guided PDT-SDT therapy, but also provides some insights for designing other PpIX-related molecules with the similar structure for bioapplication.

Bone tumors, particularly osteosarcoma, are prevalent among children and adolescents. This ailment has emerged as the second most frequent cause of cancer-related mortality in adolescents. Conventional treatment methods comprise extensive surgical resection, radiotherapy, and chemotherapy. Consequently, the management of bone tumors and bone regeneration poses significant clinical challenges. Photothermal tumor therapy has attracted considerable attention owing to its minimal invasiveness and high selectivity. However, key challenges have limited its widespread clinical use. Enhancing the tumor specificity of photosensitizers through targeting or localized activation holds potential for better outcomes with fewer adverse effects. Combinations with chemotherapies or immunotherapies also present avenues for improvement. In this review, we provide an overview of the most recent strategies aimed at overcoming the limitations of photothermal therapy (PTT), along with current research directions in the context of bone tumors, including (1) target strategies, (2) photothermal therapy combined with multiple therapies (immunotherapies, chemotherapies, and chemodynamic therapies, magnetic, and photodynamic therapies), and (3) bifunctional scaffolds for photothermal therapy and bone regeneration. We delve into the pros and cons of these combination methods and explore current research focal points. Lastly, we address the challenges and prospects of photothermal combination therapy.

Given the scarcity of novel antibiotics, the eradication of bacterial biofilm infections poses formidable challenges. Upon bacterial infection, the host restricts Fe ions, which are crucial for bacterial growth and maintenance. Having coevolved with the host, bacteria developed adaptive pathways like the hemin-uptake system to avoid iron deficiency. Inspired by this, we propose a novel strategy, termed iron nutritional immunity therapy (INIT), utilizing Ga-CT@P nanocomposites constructed with gallium, copper-doped tetrakis (4-carboxyphenyl) porphyrin (TCPP) metal-organic framework, and polyamine-amine polymer dots, to target bacterial iron intakes and starve them. Owing to the similarity between iron/hemin and gallium/TCPP, gallium-incorporated porphyrin potentially deceives bacteria into uptaking gallium ions and concurrently extracts iron ions from the surrounding bacteria milieu through the porphyrin ring. This strategy orchestrates a "give and take" approach for Ga3+/Fe3+ exchange. Simultaneously, polymer dots can impede bacterial iron metabolism and serve as real-time fluorescent iron-sensing probes to continuously monitor dynamic iron restriction status. INIT based on Ga-CT@P nanocomposites induced long-term iron starvation, which affected iron-sulfur cluster biogenesis and carbohydrate metabolism, ultimately facilitating biofilm eradication and tissue regeneration. Therefore, this study presents an innovative antibacterial strategy from a nutritional perspective that sheds light on refractory bacterial infection treatment and its future clinical application.

Seasonal influenza still greatly threatens public health worldwide, leading to significant morbidity and mortality. Antiviral medications for influenza treatment are limited and accompanied by increased drug resistance. In severe influenza virus infection, hyperinflammation and hypoxia may be the significant threats associated with mortality, so the development of effective therapeutic methods to alleviate excessive inflammation while reducing viral damage is highly pursued. Here, a multifunctional MOF-based nanohybrid of Cu─TCPP@Mn3 O4 as a novel drug against influenza A virus infection (MOF = metal-organic framework; TCPP = tetrakis (4-carboxyphenyl) porphyrin) is designed. Cu─TCPP@Mn3 O4 exhibits potent inhibitory capability against influenza A virus infection in vitro and in vivo. The mechanism study reveals that Cu─TCPP@Mn3 O4 inhibits the virus entry by binding to the HA2 subunit of influenza A virus hemagglutinin. In addition, the nanoparticles of Mn3 O4 in Cu─TCPP@Mn3 O4 can scavenge intracellular ROS with O2 generation to downregulate inflammatory factors and effectively inhibit cytokines production. By reconstructing the antioxidant microenvironment, Cu─TCPP@Mn3 O4 features as a promising nanomedicine with anti-inflammatory and anti-viral synergistic effects.

A nanozyme is a nanoscale material having enzyme-like properties. It exhibits several superior properties, including low preparation cost, robust catalytic activity, and long-term storage at ambient temperatures. Moreover, high stability enables repetitive use in multiple catalytic reactions. Hence, it is considered a potential replacement for natural enzymes. Enormous research interest in nanozymes in the past two decades has made it imperative to look for better enzyme-mimicking materials for biomedical applications. Given this, research on metal-organic frameworks (MOFs) as a potential nanozyme material has gained momentum. MOFs are advanced hybrid materials made of inorganic metal ions and organic ligands. Their distinct composition, adaptable pore size, structural diversity, and ease in the tunability of physicochemical properties enable MOFs to mimic enzyme-like activities and act as promising nanozyme candidates. This review aims to discuss recent advances in the development of MOF-based nanozymes (MOF-NZs) and highlight their applications in the field of biomedicine. Firstly, different enzyme-mimetic activities exhibited by MOFs are discussed, and insights are given into various strategies to achieve them. Modification and functionalization strategies are deliberated to obtain MOF-NZs with enhanced catalytic activity. Subsequently, applications of MOF-NZs in the biosensing and therapeutics domain are discussed. Finally, the review is concluded by giving insights into the challenges encountered with MOF-NZs and possible directions to overcome them in the future. With this review, we aim to encourage consolidated efforts across enzyme engineering, nanotechnology, materials science, and biomedicine disciplines to inspire exciting innovations in this emerging yet promising field.

In the last decades, near-infrared (NIR) light has attracted considerable attention due to its unique properties and numerous potential applications in bioimaging and disease treatment. Bone tissue engineering for bone regeneration with the help of biomaterials is currently an effective means of treating bone defects. As a controlled light source with deeper tissue penetration, NIR light can provide real-time feedback of key information on bone regeneration in vivo utilizing fluorescence imaging and be used for bone disease treatment. This review provides a comprehensive overview of NIR light-facilitated bone tissue engineering, from the introduction of NIR probes as well as NIR light-responsive materials, and the visualization of bone regeneration to the treatment of bone-related diseases. Furthermore, the existing challenges and future development directions of NIR light-based bone tissue engineering are also discussed. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement.

Radionuclides produce Cherenkov radiation (CR), which can potentially activate photosensitizers (PSs) in phototherapy. Several groups have studied Cherenkov energy transfer to PSs using optical imaging; however, cost-effectively identifying whether PSs are excited by radionuclide-derived CR and detecting fluorescence emission from excited PSs remain a challenge. Many laboratories face the need for expensive dedicated equipment.

To cost-effectively confirm whether PSs are excited by radionuclide-derived CR and distinguish fluorescence emission from excited PSs.

The absorbance and fluorescence spectra of PSs were measured using a microplate reader and fluorescence spectrometer to examine the photo-physical properties of PSs. To mitigate the need for expensive dedicated equipment and achieve the aim of the study, we developed a method that utilizes a charge-coupled device optical imaging system and appropriate long-pass filters of different wavelengths (manual sequential application of long-pass filters of 515, 580, 645, 700, 750, and 800 nm). Tetrakis (4-carboxyphenyl) porphyrin (TCPP) was utilized as a model PS. Different doses of copper-64 (64CuCl2) (4, 2, and 1 mCi) were used as CR-producing radionuclides. Imaging and data acquisition were performed 0.5 h after sample preparation. Differential image analysis was conducted by using ImageJ software (National Institutes of Health) to visually evaluate TCPP fluorescence.

The maximum absorbance of TCPP was at 390-430 nm, and the emission peak was at 670 nm. The CR and CR-induced TCPP emissions were observed using the optical imaging system and the high-transmittance long-pass filters described above. The emission spectra of TCPP with a peak in the 645-700 nm window were obtained by calculation and subtraction based on the serial signal intensity (total flux) difference between 64CuCl2 + TCPP and 64CuCl2. Moreover, the differential fluorescence images of TCPP were obtained by subtracting the 64CuCl2 image from the 64CuCl2 + TCPP image. The experimental results considering different 64CuCl2 doses showed a dose-dependent trend. These results demonstrate that a bioluminescence imaging device coupled with different long-pass filters and subtraction image processing can confirm the emission spectra and differential fluorescence images of CR-induced TCPP.

This simple method identifies the PS fluorescence emission generated by radionuclide-derived CR and can contribute to accelerating the development of Cherenkov energy transfer imaging and the discovery of new PSs.

Studies have reported on the significance of copper incorporated nanomaterials (CINMs) in cancer theranostics and tissue regeneration. Given their unique physicochemical properties and tunable nanostructures, CINMs are used in photothermal therapy (PTT) and photothermal-derived combination therapies. They have the potential to overcome the challenges of unsatisfactory efficacy of conventional therapies in an efficient and non-invasive manner. This review summarizes the recent advances in CINMs-based PTT in biomedicine. First, the classification and structure of CINMs are introduced. CINMs-based PTT combination therapy in tumors and PTT guided by multiple imaging modalities are then reviewed. Various representative designs of CINMs-based PTT in bone, skin and other organs are presented. Furthermore, the biosafety of CINMs is discussed. Finally, this analysis delves into the current challenges that researchers face and offers an optimistic outlook on the prospects of clinical translational research in this field. This review aims at elucidating on the applications of CINMs-based PTT and derived combination therapies in biomedicine to encourage future design and clinical translation.

Malignant bone tumors are characterized by severe disability rate, mortality rate, and heavy recurrence rate owing to the complex pathogenesis and insidious disease progression, which seriously affect the terminal quality of patients' lives. Photothermal therapy (PTT) has emerged as an attractive adjunctive treatment offering prominent hyperthermal therapeutic effects to enhance the effectiveness of surgical treatment and avoid recurrence. Simultaneously, various advanced biomaterials with photothermal capacity are currently created to address malignant bone tumors, performing distinctive biological functions, including nanomaterials, bioceramics (BC), polymers, and hydrogels et al. Furthermore, PTT-related combination therapeutic strategies can provide more significant curative benefits by reducing drug toxicity, improving tumor-killing efficiency, stimulating anti-cancer immunity, and improving immune sensitivity relative to monotherapy, even in complex tumor microenvironments (TME). This review summarizes the current advanced biomaterials applicable in PTT and relevant combination therapies on malignant bone tumors for the first time. The multiple choices of advanced biomaterials, treatment methods, and new prospects for future research in treating malignant bone tumors with PTT are generalized to provide guidance. Malignant bone tumors seriously affect the terminal quality of patients' lives. Photothermal therapy (PTT) has emerged as an attractive adjunctive treatment enhancing the effectiveness of surgical treatment and avoiding recurrence. In this review, advanced biomaterials applicable in the PTT of malignant bone tumors and their distinctive biological functions are comprehensively summarized for the first time. Simultaneously, multiple PTT-related combination therapeutic strategies are classified to optimize practical clinical issues, contributing to the selection of biomaterials, therapeutic alternatives, and research perspectives for the adjuvant treatment of malignant bone tumors with PTT in the future.

Metal-organic frameworks (MOFs) have received extensive attention in tumor therapy because of their advantages, including large specific surface area, regular pore size, adjustable shape, and facile functionalization. MOFs are porous materials formed by the coordination bonding of metal clusters and organic ligands. This review summarized the most recent advancements in tumor treatment based on nMOFs. First, we discuss the classification of MOFs, which primarily include the series of isoreticular MOF (IRMOF), zeolitic imidazolate framework (ZIF), coordination pillared-layer (CPL), Materials of Institute Lavoisier (MIL), porous coordination network (PCN), University of Oslo (UiO) and Biological metal-organic frameworks (BioMOFs). Then, we discuss the use of nMOFs in antitumor therapy, including drug delivery strategies, photodynamic therapy (PDT), photothermal therapy (PTT), and combination therapy. Finally, the obstacles and opportunities in nMOFs are discussed.

It is well known that metal-organic framework (MOF) nanostructures have unique characteristics such as high porosity, large surface areas and adjustable functionalities, so they are ideal candidates for developing drug delivery systems (DDSs) as well as theranostic platforms in cancer treatment. Despite the large number of MOF nanostructures that have been discovered, conventional MOF-derived nanosystems only have a single biofunctional MOF source with poor colloidal stability. Accordingly, developing core-shell MOF nanostructures with good colloidal stability is a useful method for generating efficient drug delivery, multimodal imaging and synergistic therapeutic systems. The preparation of core-shell MOF nanostructures has been done with a variety of materials, but inorganic nanoparticles (NPs) are highly effective for drug delivery and imaging-guided tumor treatment. Herein, we aimed to overview the synthesis of core-shell inorganic NP@MOF nanostructures followed by the application of core-shell MOFs derived from magnetic, quantum dots (QDs), gold (Au), and gadolinium (Gd) NPs in drug delivery and imaging-guided tumor treatment. Afterward, we surveyed different factors affecting prolonged drug delivery and cancer therapy, cellular uptake, biocompatibility, biodegradability, and enhanced permeation and retention (EPR) effect of core-shell MOFs. Last but not least, we discussed the challenges and the prospects of the field. We envision this article may hold great promise in providing valuable insights regarding the application of hybrid nanostructures as promising and potential candidates for multimodal imaging-guided combination cancer therapy.

Porphyrin-based antibacterial photodynamic therapy (aPDT) has found widespread applications in treating periodontitis. However, its clinical use is limited by poor energy absorption, resulting in limited reactive oxygen species (ROS) generation. To overcome this challenge, a novel Z-scheme heterostructured nanocomposite of Bi2 S3 /Cu-TCPP is developed. This nanocomposite exhibits highly efficient light absorption and effective electron-hole separation, thanks to the presence of heterostructures. The enhanced photocatalytic properties of the nanocomposite facilitate effective biofilm removal. Theoretical calculations confirm that the interface of the Bi2 S3 /Cu-TCPP nanocomposite readily adsorbs oxygen molecules and hydroxyl radicals, thereby improving ROS production rates. Additionally, the photothermal treatment (PTT) using Bi2 S3 nanoparticles promotes the release of Cu2+ ions, enhancing the chemodynamic therapy (CDT) effect and facilitating the eradication of dense biofilms. Furthermore, the released Cu2+ ions deplete glutathione in bacterial cells, weakening their antioxidant defense mechanisms. The synergistic effect of aPDT/PTT/CDT demonstrates potent antibacterial activity against periodontal pathogens, particularly in animal models of periodontitis, resulting in significant therapeutic effects, including inflammation alleviation and bone preservation. Therefore, this design of semiconductor-sensitized energy transfer represents an important advancement in improving aPDT efficacy and the treatment of periodontal inflammation.

Near-infrared (NIR) organic small molecule dyes (OSMDs) are effective photothermal agents for photothermal therapy (PTT) due to their advantages of low cost and toxicity, good biodegradation, and strong NIR absorption over a wide wavelength range. Nevertheless, OSMDs have limited applicability in PTT due to their low photothermal conversion efficiency and inadequate destruction of tumor regions that are nonirradiated by NIR light. However, they can also act as photosensitizers (PSs) to produce reactive oxygen species (ROS), which can be further eradicated by using ROS-related therapies to address the above limitations of PTT. In this review, the synergistic mechanism, composition, and properties of photodynamic therapy (PDT)-PTT nanoplatforms were comprehensively discussed. In addition, some specific strategies for further improving the combined PTT and PDT based on OSMDs for cancer to completely eradicate cancer cells were outlined. These strategies include performing image-guided co-therapy, enhancing tumor infiltration, increasing H2O2 or O2 in the tumor microenvironment, and loading anticancer drugs onto nanoplatforms to enable combined therapy with phototherapy and chemotherapy. Meanwhile, the intriguing prospects and challenges of this treatment modality were also summarized with a focus on the future trends of its clinical application.

Nanotechnology, an emerging and promising therapeutic tool, may improve the effectiveness of phototherapy (PT) in antitumor therapy because of the development of nanomaterials (NMs) with light-absorbing properties. The tumor-targeted PTs, such as photothermal therapy (PTT) and photodynamic therapy (PDT), transform light energy into heat and produce reactive oxygen species (ROS) that accumulate at the tumor site. The increase in ROS levels induces oxidative stress (OS) during carcinogenesis and disease development. Because of the localized surface plasmon resonance (LSPR) feature of copper (Cu), a vital trace element in the human body, Cu-based NMs can exhibit good near-infrared (NIR) absorption and excellent photothermal properties. In the tumor microenvironment (TME), Cu2+ combines with H2O2 to produce O2 that is reduced to Cu1+ by glutathione (GSH), causing a Fenton-like reaction that reduces tumor hypoxia and simultaneously generates ROS to eliminate tumor cells in conjunction with PTT/PDT. Compared with other therapeutic modalities, PTT/PDT can precisely target tumor location to kill tumor cells. Moreover, multiple treatment modalities can be combined with PTT/PDT to treat a tumor using Cu-based NMs. Herein, we reviewed and briefly summarized the mechanisms of actions of tumor-targeted PTT/PDT and the role of Cu, generated from Cu-based NMs, in PTs. Furthermore, we described the Cu-based NMs used in PTT/PDT applications.

With the promotion of nanochemistry research, large numbers of nanomaterials have been applied in vivo to produce desirable cytotoxic substances in response to endogenous or exogenous stimuli for achieving disease-specific therapy. However, the performance of nanomaterials is a critical issue that is difficult to improve and optimize under biological conditions. Defect-engineered nanoparticles have become the most researched hot materials in biomedical applications recently due to their excellent physicochemical properties, such as optical properties and redox reaction capabilities. Importantly, the properties of nanomaterials can be easily adjusted by regulating the type and concentration of defects in the nanoparticles without requiring other complex designs. Therefore, this tutorial review focuses on biomedical defect engineering and briefly discusses defect classification, introduction strategies, and characterization techniques. Several representative defective nanomaterials are especially discussed in order to reveal the relationship between defects and properties. A series of disease treatment strategies based on defective engineered nanomaterials are summarized. By summarizing the design and application of defective engineered nanomaterials, a simple but effective methodology is provided for researchers to design and improve the therapeutic effects of nanomaterial-based therapeutic platforms from a materials science perspective.

Rationale: Myocardial injury triggers intense oxidative stress, inflammatory response, and cytokine release, which are essential for myocardial repair and remodeling. Excess reactive oxygen species (ROS) scavenging and inflammation elimination have long been considered to reverse myocardial injuries. However, the efficacy of traditional treatments (antioxidant, anti-inflammatory drugs and natural enzymes) is still poor due to their intrinsic defects such as unfavorable pharmacokinetics and bioavailability, low biological stability, and potential side effects. Nanozyme represents a candidate to effectively modulate redox homeostasis for the treatment of ROS related inflammation diseases. Methods: We develop an integrated bimetallic nanozyme derived from metal-organic framework (MOF) to eliminate ROS and alleviate inflammation. The bimetallic nanozyme (Cu-TCPP-Mn) is synthesized by embedding manganese and copper into the porphyrin followed by sonication, which could mimic the cascade activities of superoxide dismutase (SOD) and catalase (CAT) to transform oxygen radicals to hydrogen peroxide, followed by the catalysis of hydrogen peroxide into oxygen and water. Enzyme kinetic analysis and oxygen-production velocities analysis were performed to evaluate the enzymatic activities of Cu-TCPP-Mn. We also established myocardial infarction (MI) and myocardial ischemia-reperfusion (I/R) injury animal models to verify the ROS scavenging and anti-inflammation effect of Cu-TCPP-Mn. Results: As demonstrated by kinetic analysis and oxygen-production velocities analysis, Cu-TCPP-Mn nanozyme possesses good performance in both SOD- and CAT-like activities to achieve synergistic ROS scavenging effect and provide protection for myocardial injury. In both MI and I/R injury animal models, this bimetallic nanozyme represents a promising and reliable technology to protect the heart tissue from oxidative stress and inflammation-induced injury, and enables the myocardial function to recover from otherwise severe damage. Conclusions: This research provides a facile and applicable method to develop a bimetallic MOF nanozyme, which represents a promising alternative to the treatment of myocardial injuries.

The simulation of neurons receiving stimulation and transmitting signals by proton conduction has great potential applications in electrochemistry and biology. In this work, copper tetrakis(4-carboxyphenyl)porphyrin (Cu-TCPP), which is a proton conductive metal organic framework (MOF) with photothermal response, is adopted as the structural framework, with the in situ co-incorporation of polystyrene sulfonate (PSS) and sulfonated spiropyran (SSP) to prepare the composite membranes. The resultant PSS-SSP@Cu-TCPP thin-film membranes were used as the logic gates i.e., NO gate, NOR gate and NAND gate because of the photothermal effect of Cu-TCPP MOFs and the photoinduced conformational changes of SSP. This membrane exhibits the high proton conductivity of 1.37 × 10^-4 S cm^-1. Under the conditions of 55 °C and 95% relative humidity (RH), using 405 nm laser irradiation with 400 mW cm^-2 and 520 nm laser irradiation with 200 mW cm^-2 as inputs, the device can be adjusted between various steady states, and the value of the conductivity is regarded as the output with different thresholds in different logic gates. Before and after laser irradiation, the electrical conductivity changes dramatically, and the ON/OFF switching ratio reached 1068. The application of three logic gates is realized by constructing circuits with LED lights. Depending on the convenience of light and the easy measurement of conductivity, this kind of device with light source as input and electrical signal as output provides the possibility to realize the remote control of chemical sensors and complex logic gates devices.

Due to radiation resistance and the immunosuppressive microenvironment of metastatic osteosarcoma, novel radiosensitizers that can sensitize radiotherapy (RT) and antitumor immunity synchronously urgently needed. Here, the authors developed a nanoscale metal-organic framework (MOF, named TZM) by co-doping high-atomic elements Ta and Zr as metal nodes and porphyrinic molecules (tetrakis(4-carboxyphenyl)porphyrin (TCPP)) as a photosensitizing ligand. Given the 3D arrays of ultra-small heavy metals, porous TZM serves as an efficient attenuator absorbing X-ray energy and sensitizing hydroxyl radical generation for RT. Ta-Zr co-doping narrowed the highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) energy gap and exhibited close energy levels between the singlet and triplet photoexcited states, facilitating TZM transfer energy to the photosensitizer TCPP to sensitize singlet oxygen (1 O2 ) generation for radiodynamic therapy (RDT). The sensitized RT-RDT effects of TZM elicit a robust antitumor immune response by inducing immunogenic cell death, promoting dendritic cell maturation, and upregulating programmed cell death protein 1 (PD-L1) expression via the cGAS-STING pathway. Furthermore, a combination of TZM, X-ray, and anti-PD-L1 treatments amplify antitumor immunotherapy and efficiently arrest osteosarcoma growth and metastasis. These results indicate that TZM is a promising radiosensitizer for the synergistic RT and immunotherapy of metastatic osteosarcoma.

Metal-organic frameworks (MOFs) hold great promise for widespread applications in biomedicine and nanomedicine. MOFs are one of the most fascinating nanocarriers for drug delivery, benefiting from their high porosity and facile modification. Furthermore, the tailored components of MOFs can be therapeutic agents for various treatments, including drugs as organic ligands of MOFs, active metal as central metal ions of MOFs, and their combinations as carrier-free MOF-based nanodrug. In this review, the advances in delivery systems and applications as therapeutic agents for nanoscale MOF-based materials are summarized. The challenges of MOFs in clinical translation and the future directions in the field of MOFs therapy are also discussed. We hope that more researchers will focus their attention on advancing and translating MOF-based nanodrugs into pre-clinical and clinical applications.

Effective and real-time detection of lactate (LA) content in human sweat has attracted considerable attention from researchers. In this work, a novel electrochemical paper-based analysis device (ePAD) was developed for the non-invasive detection of LA in sweat. The electrocatalytic properties of AuNP/Cu-TCPP(Fe) hybrid nanosheets, which were prepared by an optimised synthetic method, were studied by CV and EIS electrochemical methods for the first time and the working electrode can be fabricated using a drip coating method. The lactate sensor was optimised and validated for usability, adoptability and interpretability. To the best of our knowledge, this was the fastest, lowest detection line and widest linear range method reported to date for the detection of lactate. It achieved the detection limit of 0.91 pM and a linear range from 0.013 nM to 100 mM. The dual catalytic effects of the hybrid NSs shortened the detection time by nearly two times and enhanced the sensitivity approximately two times, an accuracy unmatched until now. Furthermore, this sensor was employed for LA analysis and validated by high performance liquid chromatography (HPLC). The ePAD shows superior biocompatibility, accuracy, and high sensitivity and can be easily manufactured. Hence, it is applicable for the long-term monitoring of sweat LA concentrations in point-of-care testing, athletic testing of athletes and military personnel and other subjects in different extreme environments.

Nano-immunotherapy has been recognized as a highly promising strategy for cancer treatment in recent decades, which combines nanotechnology and immunotherapy to combat against tumors. Hybrid nanomaterials consisting of at least two constituents with distinct compositions and properties, usually organic and inorganic, have been engineered with integrated functions and enormous potential in boosting cancer immunotherapy. This review provides a summary of hybrid nanomaterials reported for cancer immunotherapy, including nanoscale metal-organic frameworks, metal-phenolic networks, mesoporous organosilica nanoparticles, metallofullerene nanomaterials, polymer-lipid, and biomacromolecule-based hybrid nanomaterials. The combination of immunotherapy with chemotherapy, chemodynamic therapy, radiotherapy, radiodynamic therapy, photothermal therapy, photodynamic therapy, and sonodynamic therapy based on hybrid nanomaterials is also discussed. Finally, the current challenges and the prospects for designing hybrid nanomaterials and their application in cancer immunotherapy are outlined.

Cancer is a complex disease associated with a combination of abnormal physiological process and exhibiting dysfunctions in multiple systems. To provide effective treatment and diagnosis for cancer, current treatment strategies simultaneously focus on various tumor targets. Based on the rapid development of nanotechnology, nanocarriers have been shown to exhibit excellent potential for cancer therapy. Compared with nanoparticles with single functions, multifunctional nanoparticles are believed to be more aggressive and potent in the context of tumor targeting. However, the development of multifunctional nanoparticles is not simply an upgraded version of the original function, but involves a sophisticated system with a proper backbone, optimized modification sites, simple preparation method, and efficient function integration. Despite this, many well-designed multifunctional nanoparticles with promising therapeutic potential have emerged recently. Here, to give a detailed understanding and analyzation of the currently developed multifunctional nanoparticles, their platform structures with organic or inorganic backbones were systemically generalized. We emphasized on the functionalization and modification strategies, which provide additional functions to the nanoparticle. We also discussed the application combination strategies that were involved in the development of nanoformulations with functional crosstalk. This review thus provides an overview of the construction strategies and application advances of multifunctional nanoparticles.

Despite the significant improvement in the survival rate of cancer patients, the total cure of bone cancer is still a knotty clinical challenge. Traditional surgical resectionof bone tumors is less than satisfactory, which inevitably results in bone defects and the inevitable residual tumor cells. For the purpose of realizing minimal invasiveness and local curative effects, photothermal therapy (PTT) under the irradiation of near-infrared light has made extensive progress in ablating tumors, and various photothermal therapeutic agents (PTAs) for the treatment of bone tumors have thus been reported in the past few years, has and have tended to focus on osteogenic bio-scaffolds modified with PTAs in order to break through the limitation that PTT lacks, osteogenic capacity. These so-called bifunctional scaffolds simultaneously ablate bone tumors and generate new tissues at the bone defects. This review summarizes the recent application progress of various bifunctional scaffolds and puts forward some practical constraints and future perspectives on bifunctional scaffolds for tumor therapy and bone regeneration: two hawks with one arrow.

Osteosarcoma is the most prevalent bone malignant tumor in children and teenagers. The bone defect, recurrence, and metastasis after surgery severely affect the life quality of patients. Clinically, bone grafts are implanted. Primary bioceramic scaffolds show a monomodal osteogenesis function. With the advances in three-dimensional printing technology and materials science, while maintaining the osteogenesis ability, scaffolds become more patient-specific and obtain additional anti-tumor ability with functional agents being loaded. Anti-tumor therapies include photothermal, magnetothermal, old and novel chemo-, gas, and photodynamic therapy. These strategies kill tumors through novel mechanisms to treat refractory osteosarcoma due to drug resistance, and some have shown the potential to reverse drug resistance and inhibit metastasis. Therefore, multifunctional three-dimensional printed bioceramic scaffolds hold excellent promise for osteosarcoma treatments. To better understand, we review the background of osteosarcoma, primary 3D-printed bioceramic scaffolds, and different therapies and have a prospect for the future.