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Keywords = synergistic phototherapy

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22 pages, 11222 KB  
Article
Multifunctional Near-Infrared-Responsive Silk Fibroin Nanomedicine for Tumor Treatment and Imaging
by Die Xu, Shanshan He, Jingzhu Xing, Li Hao, Zhijun Zhang and Miao Su
Materials 2026, 19(15), 3359; https://doi.org/10.3390/ma19153359 - 6 Aug 2026
Viewed by 256
Abstract
The complexity and heterogeneity of tumors make monotherapy inadequate for effective tumor elimination, highlighting the urgent need for multifunctional synergistic therapeutic strategies. In this study, a near-infrared (NIR)-responsive multimodal therapeutic nanoplatform (FSINPs) was constructed by simple adsorption of indocyanine green (ICG) and Fe [...] Read more.
The complexity and heterogeneity of tumors make monotherapy inadequate for effective tumor elimination, highlighting the urgent need for multifunctional synergistic therapeutic strategies. In this study, a near-infrared (NIR)-responsive multimodal therapeutic nanoplatform (FSINPs) was constructed by simple adsorption of indocyanine green (ICG) and Fe3+ onto silk fibroin nanoparticles. Molecular docking showed that ICG binds stably to silk fibroin mainly via hydrogen bonds. Density functional theory (DFT) calculations predicted that Fe3+ strongly coordinates with the sulfonate groups of ICG and quenches ICG fluorescence via intermolecular charge transfer. Under conditions mimicking the acidic and high-glutathione tumor microenvironment, the ICG-Fe3+ coordination is disrupted, leading to fluorescence recovery of FSINPs. Fe3+ catalyzes the Fenton reaction to generate hydroxyl radicals (·OH), thereby achieving chemodynamic therapy (CDT). Upon 808 nm laser irradiation, ICG acts as a dual photosensitizer capable of both photothermal therapy (PTT) and photodynamic therapy (PDT), generating local hyperthermia with a photothermal conversion efficiency as high as 48.7% and producing singlet oxygen (1O2). The photothermal effect facilitates ·OH production, and CDT enhances photodynamic efficacy. The synergistic action of the three therapeutic modalities results in potent light-activated cytotoxicity toward tumor cells. In vivo experiments demonstrated that FSINPs enable tumor microenvironment-responsive fluorescence imaging for over 48 h and achieve complete tumor eradication in a 4T1 tumor model without obvious systemic toxicity. This study provides a new strategy for constructing activatable imaging and highly synergistic PTT/CDT/PDT-integrated silk fibroin-based nanomedicines and offers computational chemistry references for their rational design and development. Full article
(This article belongs to the Section Biomaterials)
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21 pages, 4971 KB  
Review
Metal–Organic Frameworks for Precision Phototherapy of Breast Cancer
by Fan Qi, Haitao Ren, Beibei Bie, Qiaofeng Wang, Guodong Fan, Zhaona Liu, Huanle Fang and Chuanyi Wang
Molecules 2026, 31(3), 544; https://doi.org/10.3390/molecules31030544 - 4 Feb 2026
Cited by 2 | Viewed by 1405
Abstract
Breast cancer remains the most common and leading cause of cancer deaths among women worldwide. The efficacy of conventional therapies is often hampered by off-target effects and multidrug resistance. Phototherapy, encompassing photodynamic therapy (PDT) and photothermal therapy (PTT), has gained significant attention due [...] Read more.
Breast cancer remains the most common and leading cause of cancer deaths among women worldwide. The efficacy of conventional therapies is often hampered by off-target effects and multidrug resistance. Phototherapy, encompassing photodynamic therapy (PDT) and photothermal therapy (PTT), has gained significant attention due to its non-invasiveness, high spatiotemporal selectivity, and minimal side effects. However, its application is hindered by several obstacles, including the tumor hypoxic microenvironment, insufficient light penetration depth, and acquired heat resistance. Metal–organic frameworks (MOFs) have adjustable structures, enormous specific surfaces, and facile functionalization, providing an ideal platform to overcome these limitations. This review summarizes the latest research progress in the application of MOFs for precision phototherapy in breast cancer treatment. It emphasizes their role as a direct photosensitizer (PS), photothermal agent (PTA), or multifunctional nanocarrier for PDT, PTT, and synergistic phototherapy (including PDT/PTT, chemo/phototherapy, and immunotherapy/phototherapy). The design strategy and therapeutic effect of MOFs for phototherapy of breast cancer are critically discussed. In addition, the current bottlenecks and future perspectives are outlined to facilitate the clinical translation of MOF-based breast cancer treatment platforms. Full article
(This article belongs to the Special Issue Advanced Nanomaterials for Fluorescence Imaging and Phototherapy)
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12 pages, 1437 KB  
Article
Enhancement and Limitations of Green-Spectrum Dual-Wavelength Irradiation in Porphyrin-Based Antimicrobial Strategies Targeting Cutibacterium acnes subsp. elongatum
by Robin Haag, Oksana Gurow, Moritz Mack, Jörg Moisel and Martin Hessling
Pharmaceutics 2026, 18(1), 72; https://doi.org/10.3390/pharmaceutics18010072 - 5 Jan 2026
Cited by 2 | Viewed by 1111
Abstract
Background: Phototherapy utilizes targeted irradiation to inactivate bacteria or treat various medical conditions. Depending on the therapeutic goal, wavelengths from violet to infrared (IR) are applied. Within the visible and near-IR spectrum, photodynamic therapy (PDT) combines light with photosensitizers that generate reactive oxygen [...] Read more.
Background: Phototherapy utilizes targeted irradiation to inactivate bacteria or treat various medical conditions. Depending on the therapeutic goal, wavelengths from violet to infrared (IR) are applied. Within the visible and near-IR spectrum, photodynamic therapy (PDT) combines light with photosensitizers that generate reactive oxygen species (ROS), leading to bacterial inactivation. Optimizing photodynamic efficacy can involve either enhancing ROS formation through specific topical agents that modulate ROS generation or employing dual-wavelength light irradiation (DWLR) to achieve synergistic excitation. Established DWLR protocols typically combine blue and red light or IR to activate distinct photosensitizers. Materials and Methods: This study investigates whether a similar synergistic effect can be achieved within the green spectral range by simultaneously exciting a single photosensitizer—coproporphyrin III (CP III)—at 496 nm and 547 nm. Results: Convolution analysis and in vitro bacterial reduction experiments with Cutibacterium acnes subsp. elongatum revealed that cyan irradiation (496 nm) achieved the strongest photoreduction (2.31 log steps at 1620 J/cm2), whereas PC-lime irradiation (547 nm) produced a smaller effect (0.74 log steps). DWLR protocols (simultaneous and sequential irradiation) resulted in intermediate reductions (1.64 and 1.73 log steps, respectively), exceeding PC-lime but not surpassing cyan irradiation alone. Conclusions: These findings demonstrate that excitation efficiency at the local absorption maximum of CP III is the primary determinant of ROS generation, while spectral broadening through DWLR does not enhance bacterial inactivation within this wavelength range and in vitro setup. Full article
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25 pages, 905 KB  
Review
Advances in Near-Infrared BODIPY Photosensitizers: Design Strategies and Applications in Photodynamic and Photothermal Therapy
by Dorota Bartusik-Aebisher, Kacper Rogóż, Gabriela Henrykowska and David Aebisher
Pharmaceuticals 2026, 19(1), 53; https://doi.org/10.3390/ph19010053 - 26 Dec 2025
Cited by 7 | Viewed by 2321
Abstract
Background/Objectives: Boron-dipyrromethene (BODIPY) derivatives are a superior class of fluorophores prized for their exceptional photostability and tunable photophysical properties. While ideal for imaging, their translation to photodynamic therapy (PDT) has been hampered by excitation in the visible range, leading to poor tissue penetration. [...] Read more.
Background/Objectives: Boron-dipyrromethene (BODIPY) derivatives are a superior class of fluorophores prized for their exceptional photostability and tunable photophysical properties. While ideal for imaging, their translation to photodynamic therapy (PDT) has been hampered by excitation in the visible range, leading to poor tissue penetration. To overcome this, intense research has focused on developing near-infrared (NIR)-absorbing BODIPY photosensitizers (PS). This review aims to systematically summarize the hierarchical design strategies, from molecular engineering to advanced nanoplatform construction, that underpin the recent progress of NIR-BODIPY PS in therapeutic applications. Methods: We conducted a comprehensive literature review using PubMed, Scopus, and Web of Science databases. The search focused on keywords such as “BODIPY”, “aza-BODIPY”, “near-infrared”, “photodynamic therapy”, “photothermal therapy”, “nanocarriers”, “hypoxia”, “immuno-phototherapy”, and “antibacterial.” This review analyzes key studies describing molecular design, chemical modification strategies (e.g., heavy-atom effect, π-extension), nanoplatform formulation, and therapeutic applications in vitro and in vivo. Results: Our analysis reveals a clear progression in design complexity. At the molecular level, we summarize strategies to enhance selectivity, including active targeting, designing “smart” PS responsive to the tumor microenvironment (TME) (e.g., hypoxia or low pH), and precise subcellular localization (e.g., mitochondria, lysosomes). We then detail the core chemical strategies for achieving NIR absorption and high singlet oxygen yield, including π-extension, the internal heavy-atom effect, and heavy-atom-free mechanisms (e.g., dimerization). The main body of the review categorizes the evolution of advanced theranostic nanoplatforms, including targeted systems, stimuli-responsive ‘smart’ systems, photo-immunotherapy (PIT) platforms inducing immunogenic cell death (ICD), hypoxia-overcoming systems, and synergistic chemo-phototherapy carriers. Finally, we highlight emerging applications beyond oncology, focusing on the use of NIR-BODIPY PS for antibacterial therapy and biofilm eradication. Conclusions: NIR-BODIPY photosensitizers are a highly versatile and powerful class of theranostic agents. The field is rapidly moving from simple molecules to sophisticated, multifunctional nanoplatforms designed to overcome key clinical hurdles like hypoxia, poor selectivity, and drug resistance. While challenges in scalability and clinical translation remain, the rational design strategies and expanding applications, including in infectious diseases, confirm that NIR-BODIPY derivatives will be foundational to the next generation of precision photomedicine. Full article
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21 pages, 3324 KB  
Article
Curcumin and Papain-Loaded Liposomal Natural Latex Dressings with Phototherapy: A Synergistic Approach to Diabetic Wound Healing
by Franciéle M. Silva, Jaqueline R. Silva, Wellington Rodrigues, Breno A. S. M. Sousa, Thamis F. S. Gomes, Mario F. F. Rosa, Suélia S. R. F. Rosa and Marcella L. B. Carneiro
Pharmaceuticals 2025, 18(7), 1067; https://doi.org/10.3390/ph18071067 - 20 Jul 2025
Cited by 3 | Viewed by 3168
Abstract
Background: Wound healing in diabetic individuals is a prolonged process, often complicated by infections and impaired tissue regeneration. Innovative strategies combining natural bioactive compounds are needed to enhance repair. Methods: This study reports the development and characterization of natural latex-based biomembranes (NLBs) incorporated [...] Read more.
Background: Wound healing in diabetic individuals is a prolonged process, often complicated by infections and impaired tissue regeneration. Innovative strategies combining natural bioactive compounds are needed to enhance repair. Methods: This study reports the development and characterization of natural latex-based biomembranes (NLBs) incorporated with liposome-encapsulated curcumin and papain. The therapeutic efficacy of these composite dressings, in combination with red light-emitting diode (LED) phototherapy, was evaluated in a diabetic rat model. NLBs were produced by blending natural latex with multilamellar liposomes containing either curcumin, papain, or both. In vivo wound healing was assessed by applying the biomembranes to the dorsal lesions and administering red LED irradiation (650 ± 20 nm, 10 min every 48 h) over 11 days. Results: Fourier transform infrared spectroscopy (FTIR) confirmed that the integration of liposomes did not induce significant chemical alterations to the latex matrix. The treated diabetic rats exhibited enhanced wound contraction, with the curcumin and papain groups demonstrating up to 99% and 95% healing, respectively. Plasma fructosamine levels were significantly reduced (p < 0.05), indicating improved glycemic control. Conclusions: Combining NLBs with bioactive-loaded liposomes and phototherapy accelerated wound healing in diabetic rats. This multifunctional platform shows promise for the treatment of chronic wounds in diabetic patients. Full article
(This article belongs to the Section Pharmacology)
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31 pages, 5332 KB  
Review
Photothermal Release by Melanin-like Nanoparticles: Biomedical Applications
by Arianna Menichetti, Silvia Vicenzi, Agata Pane, Dario Mordini, Fabrizio Mancin and Marco Montalti
J. Funct. Biomater. 2025, 16(7), 243; https://doi.org/10.3390/jfb16070243 - 2 Jul 2025
Cited by 10 | Viewed by 4723
Abstract
Melanin-like nanoparticles (NPs) exhibit a remarkable ability to absorb light across a wide range of wavelengths, from the ultraviolet (UV) to the near-infrared (NIR) spectrum. This characteristic enables them to serve as effective photothermal agents (PTAs). Upon irradiation, especially within the NIR window, [...] Read more.
Melanin-like nanoparticles (NPs) exhibit a remarkable ability to absorb light across a wide range of wavelengths, from the ultraviolet (UV) to the near-infrared (NIR) spectrum. This characteristic enables them to serve as effective photothermal agents (PTAs). Upon irradiation, especially within the NIR window, a region where biological tissues are highly transparent, these NPs efficiently convert light energy into heat. This phenomenon, known as the photothermal effect, leads to localized temperature increases. The resulting heat can be strategically employed to induce selective cell death in photothermal therapy (PTT) or to enhance the release of therapeutic agents directly from the NPs. The inherent versatility of melanin-like NPs, stemming from their synthesis methods and the presence of various functional groups, allows for straightforward loading with drugs or other bioactive molecules. Consequently, they are attractive tools for photothermally activated release. This review paper thoroughly examines and critically discusses the latest applications of melanin-like NPs in photothermally controlled release. We dedicate a specific section to general mechanisms and approaches, and this paper concludes with an analysis of critical challenges and prospective future developments. Full article
(This article belongs to the Special Issue Nanomaterials for Drug Targeting and Drug Delivery (2nd Edition))
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35 pages, 5960 KB  
Review
The Role of Perylene Diimide Dyes as Cellular Imaging Agents and for Enhancing Phototherapy Outcomes
by Panangattukara Prabhakaran Praveen Kumar
Colorants 2025, 4(3), 22; https://doi.org/10.3390/colorants4030022 - 1 Jul 2025
Cited by 2 | Viewed by 5041
Abstract
Recent advancements in phototherapy have underscored the need for effective cellular imaging agents that can enhance therapeutic efficacy and precision. Perylene diimide (PDI) dyes, known for their unique optical properties and biocompatibility, have emerged as promising candidates in this domain. This review paper [...] Read more.
Recent advancements in phototherapy have underscored the need for effective cellular imaging agents that can enhance therapeutic efficacy and precision. Perylene diimide (PDI) dyes, known for their unique optical properties and biocompatibility, have emerged as promising candidates in this domain. This review paper provides a comprehensive analysis of the potential applications of PDI dyes in cellular imaging, specifically within the context of phototherapies. We explore the synthesis of these dyes, their photophysical characteristics, and mechanisms of cellular uptake. Moreover, this review highlights recent studies that demonstrate the effectiveness of PDI dyes in the real-time imaging of cellular processes and their synergistic effects in photodynamic therapy (PDT) and photothermal therapy (PTT). By evaluating various experimental approaches and their outcomes, we aim to elucidate the advantages of employing PDI dyes in clinical settings. The findings of this review suggest that perylene diimide dyes are not only capable of enhancing imaging contrast but also optimizing the therapeutic response in targeted phototherapy applications. Ultimately, this paper advocates for further research into the integration of PDI dyes in clinical practice, emphasizing their potential to significantly improve patient outcomes in cancer and other diseases requiring photoactive treatment modalities. Full article
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49 pages, 24112 KB  
Review
Synergistic Cancer Therapies Enhanced by Nanoparticles: Advancing Nanomedicine Through Multimodal Strategies
by Seyed Mohamad Sadegh Mousavi-Kiasary, Ahmood Senabreh, Ashkan Zandi, Rogelio Pena, Frances Cruz, Ali Adibi and Nasrin Hooshmand
Pharmaceutics 2025, 17(6), 682; https://doi.org/10.3390/pharmaceutics17060682 - 22 May 2025
Cited by 35 | Viewed by 5588
Abstract
Cancer remains a formidable global health challenge due to its complex pathophysiology and resistance to conventional treatments. In recent years, the convergence of nanotechnology and oncology has paved the way for innovative therapeutic platforms that address the limitations of traditional modalities. This review [...] Read more.
Cancer remains a formidable global health challenge due to its complex pathophysiology and resistance to conventional treatments. In recent years, the convergence of nanotechnology and oncology has paved the way for innovative therapeutic platforms that address the limitations of traditional modalities. This review examines how nanoparticle (NP)-based strategies enhance the efficacy of chemotherapy, radiotherapy, phototherapy, immunotherapy, and gene therapy by enabling targeted delivery, controlled drug release, and tumor-specific accumulation via the enhanced permeability and retention (EPR) effect. We discuss the design and functionalization of various organic, inorganic, and hybrid NPs, highlighting their roles in improving pharmacokinetics, overcoming multidrug resistance, and modulating the tumor microenvironment. Particular emphasis is placed on dual and multimodal therapies, such as chemo-phototherapy, chemo-immunotherapy, and gene-radiotherapy, that leverage nanoparticle carriers to amplify synergistic effects, minimize systemic toxicity, and improve clinical outcomes. We also explore cutting-edge advances in gene editing and personalized nanomedicine, as well as emerging strategies to address biological barriers and immunosuppressive mechanisms in the tumor niche. Despite the undeniable promise of nanoparticle-based cancer therapies, challenges related to toxicity, scalable manufacturing, regulatory oversight, and long-term biocompatibility must be overcome before they can fully enter clinical practice. By synthesizing recent findings and identifying key opportunities for innovation, this review provides insight into how nanoscale platforms are propelling the next generation of precision oncology. Full article
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33 pages, 10641 KB  
Review
Recent Advances in Nano-Drug Delivery Strategies for Chalcogen–Based Therapeutic Agents in Cancer Phototherapy
by Subhrakant Jena and Abderrazzak Douhal
Int. J. Mol. Sci. 2025, 26(10), 4819; https://doi.org/10.3390/ijms26104819 - 17 May 2025
Cited by 2 | Viewed by 2445
Abstract
Chalcogen–containing therapeutic agents (TAs), which include sulfur (S), selenium (Se), and tellurium (Te) atoms, have recently emerged as a promising class of photosensitizers (PSs) and photothermal agents (PTAs) for cancer phototherapy. The incorporation of heavier chalcogens into organic chromophores leads to visible–to–near–infrared (VIS–NIR) [...] Read more.
Chalcogen–containing therapeutic agents (TAs), which include sulfur (S), selenium (Se), and tellurium (Te) atoms, have recently emerged as a promising class of photosensitizers (PSs) and photothermal agents (PTAs) for cancer phototherapy. The incorporation of heavier chalcogens into organic chromophores leads to visible–to–near–infrared (VIS–NIR) light absorption, efficient triplet harvesting, and adequate heat and energy transfer efficiency, all of which are paramount for photodynamic therapy (PDT) and photothermal therapy (PTT). However, chalcogen–based PSs/PTAs suffer from photostability, bioavailability, and targeted delivery issues, which minimize their PDT/PTT performances. Nevertheless, significant progress in the rational design of nanoencapsulation strategies has been achieved to overcome the challenges of chalcogen–based TAs for effective phototherapeutic cancer treatment. This review highlights the recent advances (within the last five years) in nano-drug delivery approaches adapted for chalcogen–substituted PSs/PTAs for PDT, PTT, or synergistic PDT/PTT, integrating imaging and treatment. The PSs/PTAs described in this review are classified into three classes: (i) sulfur, (ii) selenium, and (iii) tellurium–containing TAs used in phototherapy applications. This review offers a comprehensive perspective on the design of chalcogen–substituted photosensitizers (PSs) and photothermal agents (PTAs), covering spectroscopic and computational characterization, nanoformulation strategies, and their roles in enhancing reactive oxygen species (ROS) generation and photothermal conversion efficiency for improved in vitro and in vivo performance. We hope this work will encourage further research into nanotechnological strategies designed to enhance the phototherapeutic efficacy of chalcogen–containing therapeutic agents. Full article
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31 pages, 2026 KB  
Review
Tumor Treatment by Nano-Photodynamic Agents Embedded in Immune Cell Membrane-Derived Vesicles
by Zhaoyang He, Yunpeng Huang, Yu Wen, Yufeng Zou, Kai Nie, Zhongtao Liu, Xiong Li, Heng Zou and Yongxiang Wang
Pharmaceutics 2025, 17(4), 481; https://doi.org/10.3390/pharmaceutics17040481 - 7 Apr 2025
Cited by 6 | Viewed by 1995
Abstract
Non-invasive phototherapy includes modalities such as photodynamic therapy (PDT) and photothermal therapy (PTT). When combined with tumor immunotherapy, these therapeutic approaches have demonstrated significant efficacy in treating advanced malignancies, thus attracting considerable attention from the scientific community. However, the progress of these therapies [...] Read more.
Non-invasive phototherapy includes modalities such as photodynamic therapy (PDT) and photothermal therapy (PTT). When combined with tumor immunotherapy, these therapeutic approaches have demonstrated significant efficacy in treating advanced malignancies, thus attracting considerable attention from the scientific community. However, the progress of these therapies is hindered by inherent limitations and potential adverse effects. Recent findings indicate that certain therapeutic strategies, including phototherapy, can induce immunogenic cell death (ICD), thereby opening new avenues for the integration of phototherapy with tumor immunotherapy. Currently, the development of biofilm nanomaterial-encapsulated drug delivery systems has reached a mature stage. Immune cell membrane-encapsulated nano-photosensitizers hold great promise, as they can enhance the tumor immune microenvironment. Based on bioengineering technology, immune cell membranes can be designed according to the tumor immune microenvironment, thereby enhancing the targeting and immune properties of nano-photosensitizers. Additionally, the space provided by the immune cell membrane allows for the co-encapsulation of immunotherapeutic agents and chemotherapy drugs, achieving a synergistic therapeutic effect. At the same time, the timing of photodynamic therapy (PDT) can be precisely controlled to regulate the action timing of both immunotherapeutic and chemotherapy drugs. This article summarizes and analyzes current research based on the aforementioned advancements. Full article
(This article belongs to the Special Issue Smart Nanomedicine for Cancer Diagnosis and Therapy)
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26 pages, 4876 KB  
Article
Microfluidic-Assisted Silk Nanoparticles Co-Loaded with Epirubicin and Copper Sulphide: A Synergistic Photothermal–Photodynamic Chemotherapy Against Breast Cancer
by Zijian Gao, Muhamad Hawari Mansor, Faith Howard, Jordan MacInnes, Xiubo Zhao and Munitta Muthana
Nanomaterials 2025, 15(3), 221; https://doi.org/10.3390/nano15030221 - 30 Jan 2025
Cited by 14 | Viewed by 3128
Abstract
Phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), has emerged as a promising non-invasive cancer treatment, addressing issues like drug resistance and systemic toxicity common in conventional breast cancer therapies. Recent research has shown that copper sulphide (CuS) nanoparticles and polydopamine (PDA) [...] Read more.
Phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), has emerged as a promising non-invasive cancer treatment, addressing issues like drug resistance and systemic toxicity common in conventional breast cancer therapies. Recent research has shown that copper sulphide (CuS) nanoparticles and polydopamine (PDA) exhibit exceptional photothermal conversion efficiency under 808 nm near-infrared (NIR) laser irradiation, making them valuable for cancer phototherapy. However, the effectiveness of PDT is limited in hypoxic tumour environments, which are common in many breast cancer types, due to its reliance on local oxygen levels. Moreover, single-modality approaches, including phototherapy, often prove insufficient for complete tumour elimination, despite their therapeutic strength. In this paper, a microfluidic-assisted approach was used to create multifunctional silk-based nanoparticles (SFNPs) encapsulating the chemotherapeutic drug Epirubicin (EPI), the PTT/PDT agent CuS, and the heat-activated, oxygen-independent alkyl radical generator AIPH for combined chemotherapy, PTT, and PDT, with a polydopamine (PDA) coating for enhanced photothermal effects and surface-bound folic acid (FA) for targeted delivery in breast cancer treatment. The synthesised CuS-EPI-AIPH@SF-PDA-FA nanoparticles achieved a controlled size of 378 nm, strong NIR absorption, and high photothermal conversion efficiency. Under 808 nm NIR irradiation, these nanoparticles selectively triggered the release of alkyl radicals and EPI, improving intracellular drug levels and effectively killing various breast cancer cell lines while demonstrating low toxicity to non-cancerous cells. We demonstrate that novel core–shell CuS-EPI-AIPH@SF-PDA-FA NPs have been successfully designed as a multifunctional nanoplatform integrating PTT, PDT, and chemotherapy for targeted, synergistic breast cancer treatment. Full article
(This article belongs to the Special Issue Emerging Nanoscale Materials for Cancer Diagnosis and Therapy)
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23 pages, 6520 KB  
Review
Advances in Pure Drug Self-Assembled Nanosystems: A Novel Strategy for Combined Cancer Therapy
by Runyan Niu, Xuexue Liu, Xian Yang, Xiao Du, Siliang Wang, Xiaolong Ma, Shaoping Yin, Lihua Shao and Jinping Zhang
Pharmaceutics 2025, 17(1), 68; https://doi.org/10.3390/pharmaceutics17010068 - 6 Jan 2025
Cited by 13 | Viewed by 3378
Abstract
Nanoparticle-based drug delivery systems hold great promise for improving the effectiveness of anti-tumor therapies. However, their clinical translation remains hindered by several significant challenges, including intricate preparation processes, limited drug loading capacity, and concerns regarding potential toxicity. In this context, pure drug-assembled nanosystems [...] Read more.
Nanoparticle-based drug delivery systems hold great promise for improving the effectiveness of anti-tumor therapies. However, their clinical translation remains hindered by several significant challenges, including intricate preparation processes, limited drug loading capacity, and concerns regarding potential toxicity. In this context, pure drug-assembled nanosystems (PDANSs) have emerged as a promising alternative, attracting extensive research interest due to their simple preparation methods, high drug loading efficiency, and suitability for large-scale industrial production. This innovative approach presents new opportunities to enhance both the safety and therapeutic efficacy of cancer treatments. This review comprehensively explores recent progress in the application of PDANSs for cancer therapy. It begins by detailing the self-assembly mechanisms and fundamental principles underlying PDANS formation. The discussion then advances to strategies for assembling single pure drug nanoparticles, as well as the co-assembly of multiple drugs. Subsequently, the review addresses the therapeutic potential of PDANSs in combination treatment modalities, encompassing diagnostic and therapeutic applications. These include combinations of chemotherapeutic agents, phototherapeutic approaches, the integration of chemotherapy with phototherapy, and the synergistic use of immunotherapy with other treatment methods. Finally, the review highlights the potential of PDANSs in advancing tumor therapy and their prospects for clinical application, providing key insights for future research aimed at optimizing this technology and broadening its utility in cancer treatment. Full article
(This article belongs to the Section Nanomedicine and Nanotechnology)
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13 pages, 2820 KB  
Article
Polydopamine Coated Nonspherical Magnetic Nanocluster for Synergistic Dual Magneto-Photothermal Cancer Therapy
by Gracia García-García, Marina Lázaro, Pedro Urquiza, Tania Romacho, Ángel V. Delgado and Guillermo R. Iglesias
Polymers 2025, 17(1), 85; https://doi.org/10.3390/polym17010085 - 31 Dec 2024
Cited by 6 | Viewed by 2126
Abstract
Local hyperthermia is gaining considerable interest due to its promising antitumor effects. In this context, dual magneto-photothermal cancer therapy holds great promise. For this purpose, the use of nanomaterials has been proposed. Therefore, the aim of this research is to develop a dual [...] Read more.
Local hyperthermia is gaining considerable interest due to its promising antitumor effects. In this context, dual magneto-photothermal cancer therapy holds great promise. For this purpose, the use of nanomaterials has been proposed. Therefore, the aim of this research is to develop a dual magneto-photothermal agent consisting of polydopamine-coated nonspherical magnetic nanoclusters. The physicochemical characterization of the nanoclusters was performed by electron microscopy, electron dispersive X-ray, dynamic light scattering, electrophoretic mobility, thermogravimetric analysis, and Fourier transform infrared spectroscopy. The biocompatibility of the nanoclusters was evaluated using human skin M1 fibroblasts. The potential of the nanoclusters as dual magneto-photothermal agents was investigated by applying an alternating magnetic field (18 kA/m and 165 kHz) and/or NIR laser (850 nm, 0.75 W/cm2). Nanoclusters showed a size of 350 nm consisting of nonspherical magnetic particles of 11 nm completely coated with polydopamine. In addition, they were superparamagnetic and did not significantly affect cell viability at concentrations below 200 µg/mL. Finally, the SAR values obtained for the nanoclusters demonstrated their suitability for magnetotherapy and phototherapy (71 and 41 W/g, respectively), with a synergistic effect when used together (176 W/g). Thus, this work has successfully developed polymeric-coated magnetic nanoclusters with the potential for dual magneto-photothermal cancer therapy. Full article
(This article belongs to the Special Issue Smart and Bio-Medical Polymers: 2nd Edition)
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12 pages, 2649 KB  
Article
Natural Phytochemical and Visible Light at Different Wavelengths Show Synergistic Antibacterial Activity against Staphylococcus aureus
by Jae-Young Jeong and You-Jin Hwang
Pharmaceutics 2024, 16(5), 612; https://doi.org/10.3390/pharmaceutics16050612 - 1 May 2024
Cited by 8 | Viewed by 3145 | Correction
Abstract
As the risk of antibiotic-resistant bacteria increases, interest in non-antibiotic treatment is also increasing. Among the methods used in non-antibiotic therapy, natural antibiotics such as essential oils have disadvantages such as low efficiency. In the case of phototherapy, the light used for antibacterial [...] Read more.
As the risk of antibiotic-resistant bacteria increases, interest in non-antibiotic treatment is also increasing. Among the methods used in non-antibiotic therapy, natural antibiotics such as essential oils have disadvantages such as low efficiency. In the case of phototherapy, the light used for antibacterial activities has low penetration into the human body because of its short wavelength, making it of low medical utility. To solve this problem, this study aimed to determine conditions for enhancing the antibacterial activity of natural phytochemicals and visible light. Four natural phytochemical extracts that showed high antibacterial properties in previous studies were analyzed. Synergistic effects on antibacterial activity and cytotoxicity were determined when natural phytochemical extracts and visible light were simultaneously used. As a result, it was confirmed that the antibacterial activity increased by four times when Sanguisorba officinalis L. was irradiated with 465 nm for 10 min and 520 nm for 40 min, and Uncaria gambir Roxb. was irradiated with 465 nm for 10 min and 520 nm for 60 min compared to when Sanguisorba officinalis L. and Uncaria gambir Roxb. were used alone. The synergistic effect on antibacterial activity was independent of the absorption peak of the natural phytochemical extracts. In addition, in the case of natural phytochemical extracts with improved antibacterial activity, it was confirmed that the improvement of antibacterial activity was increased in inverse proportion to the light irradiation wavelength and in proportion to the light irradiation time. The antibacterial activity was enhanced regardless of antibiotic resistance. In the case of cytotoxicity, it was confirmed that there was no toxicity to A549 cells when treated with 465 nm, the shortest wavelength among the natural phytochemical extracts. These results show how to replace blue light, which has been underutilized due to its low transmittance and cytotoxicity. They also demonstrate the high medical potential of using natural phytochemical and visible light as a combination therapy. Full article
(This article belongs to the Special Issue Natural Products in Photodynamic Therapy)
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23 pages, 14761 KB  
Article
Self-Assembled Matrine-PROTAC Encapsulating Zinc(II) Phthalocyanine with GSH-Depletion-Enhanced ROS Generation for Cancer Therapy
by Sitong Lai, Bing Wang, Kunhui Sun, Fan Li, Qian Liu, Xie-An Yu, Lihe Jiang and Lisheng Wang
Molecules 2024, 29(8), 1845; https://doi.org/10.3390/molecules29081845 - 18 Apr 2024
Cited by 8 | Viewed by 3049
Abstract
The integration of a multidimensional treatment dominated by active ingredients of traditional Chinese medicine (TCM), including enhanced chemotherapy and synergistically amplification of oxidative damage, into a nanoplatform would be of great significance for furthering accurate and effective cancer treatment with the active ingredients [...] Read more.
The integration of a multidimensional treatment dominated by active ingredients of traditional Chinese medicine (TCM), including enhanced chemotherapy and synergistically amplification of oxidative damage, into a nanoplatform would be of great significance for furthering accurate and effective cancer treatment with the active ingredients of TCM. Herein, in this study, we designed and synthesized four matrine-proteolysis-targeting chimeras (PROTACs) (depending on different lengths of the chains named LST-1, LST-2, LST-3, and LST-4) based on PROTAC technology to overcome the limitations of matrine. LST-4, with better anti-tumor activity than matrine, still degrades p-Erk and p-Akt proteins. Moreover, LST-4 NPs formed via LST-4 self-assembly with stronger anti-tumor activity and glutathione (GSH) depletion ability could be enriched in lysosomes through their outstanding enhanced permeability and retention (EPR) effect. Then, we synthesized LST-4@ZnPc NPs with a low-pH-triggered drug release property that could release zinc(II) phthalocyanine (ZnPc) in tumor sites. LST-4@ZnPc NPs combine the application of chemotherapy and phototherapy, including both enhanced chemotherapy from LST-4 NPs and the synergistic amplification of oxidative damage, through increasing the reactive oxygen species (ROS) by photodynamic therapy (PDT), causing an GSH decrease via LST-4 mediation to effectively kill tumor cells. Therefore, multifunctional LST-4@ZnPc NPs are a promising method for killing cancer cells, which also provides a new paradigm for using natural products to kill tumors. Full article
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