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Keywords = photosensitizer delivery system

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47 pages, 7003 KiB  
Review
Phthalocyanines Conjugated with Small Biologically Active Compounds for the Advanced Photodynamic Therapy: A Review
by Kyrylo Chornovolenko and Tomasz Koczorowski
Molecules 2025, 30(15), 3297; https://doi.org/10.3390/molecules30153297 - 6 Aug 2025
Abstract
Phthalocyanines (Pcs) are well-established photosensitizers in photodynamic therapy, valued for their strong light absorption, high singlet oxygen generation, and photostability. Recent advances have focused on covalently conjugating Pcs, particularly zinc phthalocyanines (ZnPcs), with a wide range of small bioactive molecules to improve selectivity, [...] Read more.
Phthalocyanines (Pcs) are well-established photosensitizers in photodynamic therapy, valued for their strong light absorption, high singlet oxygen generation, and photostability. Recent advances have focused on covalently conjugating Pcs, particularly zinc phthalocyanines (ZnPcs), with a wide range of small bioactive molecules to improve selectivity, efficacy, and multifunctionality. These conjugates combine light-activated reactive oxygen species (ROS) production with targeted delivery and controlled release, offering enhanced treatment precision and reduced off-target toxicity. Chemotherapeutic agent conjugates, including those with erlotinib, doxorubicin, tamoxifen, and camptothecin, demonstrate receptor-mediated uptake, pH-responsive release, and synergistic anticancer effects, even overcoming multidrug resistance. Beyond oncology, ZnPc conjugates with antibiotics, anti-inflammatory drugs, antiparasitics, and antidepressants extend photodynamic therapy’s scope to antimicrobial and site-specific therapies. Targeting moieties such as folic acid, biotin, arginylglycylaspartic acid (RGD) and epidermal growth factor (EGF) peptides, carbohydrates, and amino acids have been employed to exploit overexpressed receptors in tumors, enhancing cellular uptake and tumor accumulation. Fluorescent dye and porphyrinoid conjugates further enrich these systems by enabling imaging-guided therapy, efficient energy transfer, and dual-mode activation through pH or enzyme-sensitive linkers. Despite these promising strategies, key challenges remain, including aggregation-induced quenching, poor aqueous solubility, synthetic complexity, and interference with ROS generation. In this review, the examples of Pc-based conjugates were described with particular interest on the synthetic procedures and optical properties of targeted compounds. Full article
(This article belongs to the Section Organic Chemistry)
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29 pages, 3455 KiB  
Review
Recent Advances in Nanoparticle and Nanocomposite-Based Photodynamic Therapy for Cervical Cancer: A Review
by Dorota Bartusik-Aebisher, Mohammad A. Saad, Agnieszka Przygórzewska and David Aebisher
Cancers 2025, 17(15), 2572; https://doi.org/10.3390/cancers17152572 - 4 Aug 2025
Viewed by 123
Abstract
Cervical cancer represents a significant global health challenge. Photodynamic therapy (PDT) appears to be a promising, minimally invasive alternative to standard treatments. However, the clinical efficacy of PDT is sometimes limited by the low solubility and aggregation of photosensitizers, their non-selective distribution in [...] Read more.
Cervical cancer represents a significant global health challenge. Photodynamic therapy (PDT) appears to be a promising, minimally invasive alternative to standard treatments. However, the clinical efficacy of PDT is sometimes limited by the low solubility and aggregation of photosensitizers, their non-selective distribution in the body, hypoxia in the tumor microenvironment, and limited light penetration. Recent advances in nanoparticle and nanocomposite platforms have addressed these challenges by integrating multiple functional components into a single delivery system. By encapsulating or conjugating photosensitizers in biodegradable matrices, such as mesoporous silica, organometallic structures and core–shell construct nanocarriers increase stability in water and extend circulation time, enabling both passive and active targeting through ligand decoration. Up-conversion and dual-wavelength responsive cores facilitate deep light conversion in tissues, while simultaneous delivery of hypoxia-modulating agents alleviates oxygen deprivation to sustain reactive oxygen species generation. Controllable “motor-cargo” constructs and surface modifications improve intratumoral diffusion, while aggregation-induced emission dyes and plasmonic elements support real-time imaging and quantitative monitoring of therapeutic response. Together, these multifunctional nanosystems have demonstrated potent cytotoxicity in vitro and significant tumor suppression in vivo in mouse models of cervical cancer. Combining targeted delivery, controlled release, hypoxia mitigation, and image guidance, engineered nanoparticles provide a versatile and powerful platform to overcome the current limitations of PDT and pave the way toward more effective, patient-specific treatments for cervical malignancies. Our review of the literature summarizes studies on nanoparticles and nanocomposites used in PDT monotherapy for cervical cancer, published between 2023 and July 2025. Full article
(This article belongs to the Section Cancer Therapy)
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52 pages, 3227 KiB  
Review
Advances in Photodynamic Treatment of Precancerous and Cancerous Gynecological Diseases
by Polina Alekseeva, Vladimir Makarov, Kanamat Efendiev, Aida Gilyadova and Victor Loschenov
Cancers 2025, 17(15), 2421; https://doi.org/10.3390/cancers17152421 - 22 Jul 2025
Viewed by 406
Abstract
High mortality rates and poor quality of life result from the late-stage detection and frequent recurrence of gynecological neoplasms. Background/Objectives: The aim of this study was to conduct a systematic analysis of the energy parameters of photodynamic therapy (PDT) in the treatment [...] Read more.
High mortality rates and poor quality of life result from the late-stage detection and frequent recurrence of gynecological neoplasms. Background/Objectives: The aim of this study was to conduct a systematic analysis of the energy parameters of photodynamic therapy (PDT) in the treatment of cervical and vulvar lesions, with a focus on stimulating immune responses leading to human papillomavirus (HPV) eradication and lesion regression without adverse effects, such as thermal damage. Methods: A total of 46 peer-reviewed studies published between January 2010 and April 2024 were analyzed. These studies focused on PDT applications for cervical and vulvar lesions, sourced from Google Scholar, Scopus, and Web of Science. Results: Although PDT shows promise, significant limitations exist, such as insufficient consideration of individual tumor characteristics, restricted treatment depths, and the heterogeneous distribution and low selectivity of photosensitizer (PS) accumulation in tumors. Tumor hypoxia further reduces PDT’s effectiveness, and most studies overlook immune system activation, which is crucial for targeting HPV infections and improving antitumor responses. Conclusions: Advancing the research into PDT’s molecular and cellular mechanisms, optimizing the immune response stimulation, and improving the PS and delivery methods could enhance the safety and effectiveness of cervical and vulvar neoplasm treatments. The use of personalized PDT parameters may reduce the side effects and enhance the outcomes for patients suffering from gynecological diseases. Full article
(This article belongs to the Special Issue New Advances in the Diagnosis of Gynecological Cancer)
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32 pages, 3005 KiB  
Review
Photophysical Process of Hypocrellin-Based Photodynamic Therapy: An Efficient Antimicrobial Strategy for Overcoming Multidrug Resistance
by Pazhani Durgadevi, Koyeli Girigoswami and Agnishwar Girigoswami
Physics 2025, 7(3), 28; https://doi.org/10.3390/physics7030028 - 15 Jul 2025
Viewed by 477
Abstract
The emergence of multidrug-resistant (MDR) bacteria and biofilm-associated infections has created a significant hurdle for conventional antibiotics, prompting the exploration of alternative strategies. Photodynamic therapy (PDT), a technique that utilizes photosensitizers activated by light to produce ROS, has emerged as a beacon of [...] Read more.
The emergence of multidrug-resistant (MDR) bacteria and biofilm-associated infections has created a significant hurdle for conventional antibiotics, prompting the exploration of alternative strategies. Photodynamic therapy (PDT), a technique that utilizes photosensitizers activated by light to produce ROS, has emerged as a beacon of hope in the fight against MDR microorganisms. Among the natural photosensitizers, hypocrellins (A and B) have shown remarkable potential with their dual-mode photodynamic action, generating ROS via both Type I (electron transfer) and Type II (singlet oxygen) pathways. This unique action disrupts bacterial biofilms and inactivates MDR pathogens. The amphiphilic nature of hypocrellins further enhances their promise, enabling deep biofilm penetration and ensuring potent antibacterial effects even in hypoxic environments, surpassing the capabilities of synthetic photosensitizers. This study critically examines the antimicrobial properties of hypocrellin-based PDT, emphasizing its mechanisms, advantages over traditional antibiotics, and effectiveness against MDR pathogens. Comparative analysis with other photosensitizers, the role of nanotechnology-enhanced delivery systems, and future clinical applications are explored. Its combination with nanotechnology enhances therapeutic outcomes, providing a viable alternative to conventional antibiotics. Further clinical research is essential to optimize its application and integration into antimicrobial treatment protocols. Full article
(This article belongs to the Section Biophysics and Life Physics)
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16 pages, 2228 KiB  
Article
Quantitative Fluorescence Imaging of Chemophototherapy Drug Pharmacokinetics Using Laparoscopic SFDI
by Rasel Ahmmed, Elias Kluiszo, Semra Aygun-Sunar, Matthew Willadsen, Hilliard L. Kutscher, Jonathan F. Lovell and Ulas Sunar
Int. J. Mol. Sci. 2025, 26(12), 5571; https://doi.org/10.3390/ijms26125571 - 11 Jun 2025
Viewed by 487
Abstract
Chemophototherapy (CPT) is an emerging cancer treatment that leverages the synergistic effects of photodynamic therapy (PDT) and chemotherapy. This approach utilizes photosensitizers like Porphyrin-Phospholipid (PoP) and combined with chemotherapeutic like Doxorubicin (Dox) to enable light-triggered drug release and targeted tumor destruction. Here, we [...] Read more.
Chemophototherapy (CPT) is an emerging cancer treatment that leverages the synergistic effects of photodynamic therapy (PDT) and chemotherapy. This approach utilizes photosensitizers like Porphyrin-Phospholipid (PoP) and combined with chemotherapeutic like Doxorubicin (Dox) to enable light-triggered drug release and targeted tumor destruction. Here, we present the validation of a wide-field laparoscopic spatial frequency domain imaging (SFDI) system in an ovarian cancer model. The system allows quantitative fluorescence imaging to obtain absolute drug concentrations in vivo to obtain the absolute concentrations of PoP and Dox fluorescence by correcting for tissue absorption and scattering effects. Fluorescence imaging revealed a significant reduction (~25%, p < 0.001) in PoP concentration in tumor regions post-illumination, demonstrating PDT-mediated photobleaching. Next, the Dox release experiment showed an increase of ~13 µg/mL Dox concentration at the local site. The ability to quantify both PoP and Dox fluorescence concentrations with a laparoscopic system underscores its potential for intraoperative monitoring of CPT efficacy. These findings indicate wide-field laparoscopic SFDI as a promising tool for guiding minimally invasive PDT and targeted drug delivery in preclinical and future clinical settings. Full article
(This article belongs to the Special Issue Photodynamic Therapy and Photodetection, 2nd Edition)
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18 pages, 671 KiB  
Review
Evaluating the Efficacy of Rose Bengal as a Photosensitizer in Antimicrobial Photodynamic Therapy Against Candida albicans: A Systematic Review
by Jakub Fiegler-Rudol, Barbara Lipka, Katarzyna Kapłon, Magdalena Moś, Dariusz Skaba, Aleksandra Kawczyk-Krupka and Rafał Wiench
Int. J. Mol. Sci. 2025, 26(11), 5034; https://doi.org/10.3390/ijms26115034 - 23 May 2025
Viewed by 784
Abstract
Candida albicans is a significant pathogen in various fungal infections, including oral candidiasis and denture stomatitis. As antifungal resistance rises globally, there is an urgent need for alternative treatment strategies. Antimicrobial photodynamic therapy (aPDT), utilizing a photosensitizer and light to produce reactive oxygen [...] Read more.
Candida albicans is a significant pathogen in various fungal infections, including oral candidiasis and denture stomatitis. As antifungal resistance rises globally, there is an urgent need for alternative treatment strategies. Antimicrobial photodynamic therapy (aPDT), utilizing a photosensitizer and light to produce reactive oxygen species (ROS), has emerged as a promising approach. Rose Bengal (RB), a xanthene dye, exhibits a high singlet oxygen quantum yield, making it a candidate for aPDT. However, its efficacy in C. albicans treatment has been inconsistent, particularly against biofilm-associated infections, which are more resistant to conventional therapies. This systematic review evaluates the efficacy of Rose Bengal-mediated aPDT in combating C. albicans infections by synthesizing data from studies conducted over the past decade. We focus on the effectiveness of RB across different experimental conditions, including planktonic and biofilm forms of C. albicans. The review also explores the synergy between RB and other agents, such as potassium iodide, and compares the outcomes of RB-mediated aPDT to other photosensitizers and conventional antifungal treatments. Despite its potential, RB-aPDT shows variable effectiveness due to differences in experimental protocols, such as the photosensitizer concentration, incubation times, and light parameters. The review identifies the key limitations, such as RB’s poor biofilm penetration and high dark toxicity at elevated concentrations, which hinder its clinical applicability. The combination of RB with potassium iodide enhances its antifungal efficacy, suggesting that further optimization could improve its clinical potential. Overall, while Rose Bengal-mediated aPDT holds promise as a novel antifungal treatment, further research is needed to standardize protocols, enhance delivery systems, and validate its efficacy in vivo and clinical settings. Full article
(This article belongs to the Special Issue Photodynamic Therapy and Photodetection, 2nd Edition)
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23 pages, 7191 KiB  
Article
Interleukin-15Rα-Sushi-Fc Fusion Protein Co-Hitchhikes Interleukin-15 and Pheophorbide A for Cancer Photoimmunotherapy
by Zhe Li, Jiaojiao Xu, Hongzheng Lin, Sheng Yu, Jingwen Sun, Chen Zhang, Sihang Zhang, Tingting Li, Afeng Yang and Wei Lu
Pharmaceutics 2025, 17(5), 615; https://doi.org/10.3390/pharmaceutics17050615 - 5 May 2025
Viewed by 611
Abstract
Background: Interleukin-15 (IL-15) stimulates the proliferation of natural killer cells or T cells, which, in combination with photodynamic therapy (PDT), has emerged as an effective strategy for cancer photoimmunotherapy. Instead of direct cytokine receptor activation, IL-15 necessitates first binding to the IL-15 [...] Read more.
Background: Interleukin-15 (IL-15) stimulates the proliferation of natural killer cells or T cells, which, in combination with photodynamic therapy (PDT), has emerged as an effective strategy for cancer photoimmunotherapy. Instead of direct cytokine receptor activation, IL-15 necessitates first binding to the IL-15 receptor α chain subunit (IL-15Rα), followed by trans-presentation to the IL-15 receptor β/γ chain subunit on the effector cells for pharmacologic activation. Therefore, the delivery of IL-15 remains a major challenge owing to its short half-life, its lack of targeting activity, and the limited availability of IL-15Rα. Methods: A co-hitchhiking delivery approach using recombinant IL-15 (rIL-15) and a photosensitizer, pheophorbide A (PhA), is developed for enhanced combinatorial cancer immunotherapy with PDT. A recombinant IL-15Rα-sushi-Fc fusion protein (rILR-Fc) is designed to load rIL-15 through the IL-15Rα sushi domain, which mimics its trans-presentation. Moreover, the Fc moiety of rILR-Fc can load PhA based on its high binding affinity. Results: Through self-assembly, rILR-Fc/PhA/rIL-15 nanoparticles (NPs) are formulated to co-hitchhike PhA and rIL-15, which improves the tumor accumulation of PhA and rIL-15 through receptor-mediated transcytosis. Moreover, the nanoparticles prolong the blood half-life of rIL-15 but do not alter the elimination rate of PhA from the blood. The rILR-Fc/PhA/rIL-15 NPs effectively elicit potent systemic antitumor immunity and long-lasting immune memory against tumor rechallenge in model mice bearing orthotopic colon tumors. Conclusions: The enhanced antitumor therapeutic effect demonstrates that the co-hitchhiking delivery strategy, optimizing the pharmacokinetics of both the photosensitizer and IL-15, provides a promising strategy for combinatorial photodynamic and IL-15 immunotherapy. Full article
(This article belongs to the Section Nanomedicine and Nanotechnology)
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14 pages, 7525 KiB  
Article
Novel Molecular Weight Gradient Hyaluronate Dissolving Microneedles for Sustained Intralesional Delivery and Photodynamic Activation of Hematoporphyrin in Port-Wine Stain Therapy
by Xueli Peng, Chenxin Yan, Nengquan Fan, Chaoguo Sun, Suohui Zhang and Yunhua Gao
Polymers 2025, 17(9), 1238; https://doi.org/10.3390/polym17091238 - 1 May 2025
Viewed by 545
Abstract
Port-wine stain (PWS), a progressive congenital vascular malformation characterized by ectatic dermal capillaries, demonstrates age-dependent lesion expansion and chromatic intensification, resulting in significant psychosocial comorbidity. While systemic hematoporphyrin (HP) administration remains the clinical paradigm for photodynamic therapy (PDT), its therapeutic utility is severely [...] Read more.
Port-wine stain (PWS), a progressive congenital vascular malformation characterized by ectatic dermal capillaries, demonstrates age-dependent lesion expansion and chromatic intensification, resulting in significant psychosocial comorbidity. While systemic hematoporphyrin (HP) administration remains the clinical paradigm for photodynamic therapy (PDT), its therapeutic utility is severely constrained by non-targeted biodistribution. Pharmacokinetic analyses reveal prolonged dermal retention and suboptimal lesion accumulation, predisposing 42% of patients to phototoxic reactions. To address these limitations, this work creatively suggested a local targeted drug delivery method based on soluble microneedles in response to the difficulties mentioned above. The rational design of a molecular weight (MW) HA gradient system enabled the engineering of ternary nanocomposite microneedles with enhanced biomechanical integrity (0.49 N/needle) and superior HP loading capacity, which collectively facilitated spatiotemporally controlled transdermal delivery of hematoporphyrin with complete dissolution within 30 min. The release performance, skin permeability, and storage stability of hematoporphyrin dissolving microneedles (HP-DMNs) have all been demonstrated in vitro. This study applies soluble microneedle technology to the delivery of HP in PWS for the first time. It avoids the risk of systemic exposure through precise local administration. It uses the rapid dissolution properties of microneedles to achieve high concentration and rapid release of drugs in skin lesions. This study provides a new strategy for sustained intralesional release and rapid drug delivery treatment of PWS and provides novel ideas for the development of new formulations of HP and related photosensitizers. Full article
(This article belongs to the Special Issue Polymers and Their Role in Drug Delivery, 2nd Edition)
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24 pages, 1250 KiB  
Review
Breaking the Resistance: Photodynamic Therapy in Cancer Stem Cell-Driven Tumorigenesis
by Sheeja S. Rajan, J. P. Jose Merlin and Heidi Abrahamse
Pharmaceutics 2025, 17(5), 559; https://doi.org/10.3390/pharmaceutics17050559 - 24 Apr 2025
Cited by 1 | Viewed by 742
Abstract
Cancer stem cells (CSCs) are essential for the growth of malignancies because they encourage resistance to cancer therapy and make metastasis and relapse easier. To effectively tackle the obstacles presented by CSCs, novel therapeutic approaches are required. Photodynamic therapy (PDT) is a promising [...] Read more.
Cancer stem cells (CSCs) are essential for the growth of malignancies because they encourage resistance to cancer therapy and make metastasis and relapse easier. To effectively tackle the obstacles presented by CSCs, novel therapeutic approaches are required. Photodynamic therapy (PDT) is a promising treatment option for cancer cells, which uses light-sensitive medications that are activated by light wavelengths. This review investigates the use of PDT to overcome malignancies driven by CSCs that have innate resistance mechanisms. PDT works by causing tumor cells to accumulate photosensitizers (PSs) selectively. The reactive oxygen species (ROS), which kill cells, are released by these PSs when they are stimulated by light. According to recent developments in PDT, its efficacy may go beyond traditional tumor cells, providing a viable remedy for the resistance shown by CSCs. Researchers want to improve the targeted elimination and selective targeting of CSCs by combining PDT with new PSs and customized delivery systems. Studies emphasize how PDT affects CSCs as well as bulk tumor cells. According to studies, PDT not only limits CSC growth but also modifies their microenvironment, which lowers the possibility of recovery. Additionally, studies are being conducted on the utilization of PDT and immunotherapeutic techniques to improve treatment efficacy and overcome inherent resistance of CSCs. In conclusion, PDT is a viable strategy for treating carcinogenesis driven by CSCs. By applying the most recent advancements in PDT technologies and recognizing how it interacts with CSCs, this treatment has the potential to surpass traditional resistance mechanisms and improve the future of cancer patients. Clinical and preclinical studies highlight that combining PDT with CSC-targeted approaches has the potential to overcome current therapy limitations. Future efforts should focus on clinical validation, optimizing light delivery and PS use, and developing effective combination strategies to target CSCs. Full article
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31 pages, 2026 KiB  
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
Viewed by 707
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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18 pages, 4897 KiB  
Article
Zein Nanoparticles Loaded with Vitis vinifera L. Grape Pomace Extract: Synthesis and Characterization
by Ana Guadalupe Luque-Alcaraz, Jesús Antonio Maldonado-Arriola, Pedro Amado Hernández-Abril, Mario Enrique Álvarez-Ramos and Cynthia Nazareth Hernández-Téllez
Nanomaterials 2025, 15(7), 539; https://doi.org/10.3390/nano15070539 - 2 Apr 2025
Cited by 1 | Viewed by 629
Abstract
This study investigates the synthesis and characterization of zein nanoparticles (ZNp) loaded with grape pomace extract (GPE) from Vitis vinifera L. for applications in controlled release and antioxidant delivery. Grape pomace, a byproduct of the winemaking industry, is rich in bioactive compounds, including [...] Read more.
This study investigates the synthesis and characterization of zein nanoparticles (ZNp) loaded with grape pomace extract (GPE) from Vitis vinifera L. for applications in controlled release and antioxidant delivery. Grape pomace, a byproduct of the winemaking industry, is rich in bioactive compounds, including phenols and flavonoids, which possess antioxidant properties. To overcome the limitations of these compounds, such as photosensitivity and thermal degradation, they were incorporated into zein nanoparticles using the antisolvent technique. The physicochemical properties of the ZNp-GPE system were thoroughly characterized, including size, morphology, ζ-potential, and total phenol content. Results showed high encapsulation efficiency (89–97%) and favorable loading capacities. Characterization techniques, such as scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and dynamic light scattering (DLS), confirmed that GPE was successfully incorporated into the nanoparticles, thereby enhancing their antioxidant properties. The encapsulation process did not significantly alter the spherical morphology of the nanoparticles, and loading GPE resulted in a decrease in particle size. Total phenol content analysis showed that the ZNp-GPE nanoparticles effectively retained these compounds, confirming their potential as efficient delivery systems for antioxidants. This approach not only provides a method for protecting and enhancing the bioavailability of natural antioxidants but also contributes to the valorization of agricultural waste, promoting sustainability in bio-based industries. Full article
(This article belongs to the Special Issue Nanomaterials in Medicine and Healthcare)
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20 pages, 1761 KiB  
Review
Nanoparticles for Photodynamic Therapy of Breast Cancer: A Review of Recent Studies
by Dorota Bartusik-Aebisher, Agnieszka Przygórzewska, Paweł Woźnicki and David Aebisher
Molecules 2025, 30(7), 1571; https://doi.org/10.3390/molecules30071571 - 31 Mar 2025
Cited by 1 | Viewed by 1638
Abstract
Photodynamic therapy (PDT) is a therapeutic method based on the interaction between light and a photosensitizer. Supported by nanoparticles, this method represents a promising interdisciplinary approach for the treatment of many diseases. This article reviews the latest 2024 developments in the design and [...] Read more.
Photodynamic therapy (PDT) is a therapeutic method based on the interaction between light and a photosensitizer. Supported by nanoparticles, this method represents a promising interdisciplinary approach for the treatment of many diseases. This article reviews the latest 2024 developments in the design and applications of nanoparticles dedicated to stand-alone PDT of breast cancer. Strategies to improve therapeutic efficacy by enhancing reactive oxygen species (ROS) production, precise delivery of photosensitizers and their stabilization in the systemic circulation are discussed, among others. Results from preclinical studies indicate significant improvements in therapeutic efficacy, including inhibition of tumor growth, reduction in metastasis and improvement of the immune microenvironment. The potential of these technologies to expand PDT applications in medicine and the need for further clinical trials to confirm their safety and efficacy are highlighted. Full article
(This article belongs to the Special Issue Molecular Approaches to Drug Discovery and Development)
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33 pages, 3147 KiB  
Review
Fighting Cancer with Photodynamic Therapy and Nanotechnologies: Current Challenges and Future Directions
by Laura Marinela Ailioaie, Constantin Ailioaie and Gerhard Litscher
Int. J. Mol. Sci. 2025, 26(7), 2969; https://doi.org/10.3390/ijms26072969 - 25 Mar 2025
Cited by 3 | Viewed by 1928
Abstract
Photodynamic therapy (PDT) is an innovative treatment that has recently been approved for clinical use and holds promise for cancer patients. It offers several benefits, such as low systemic toxicity, minimal invasiveness, and the ability to stimulate antitumor immune responses. For certain types [...] Read more.
Photodynamic therapy (PDT) is an innovative treatment that has recently been approved for clinical use and holds promise for cancer patients. It offers several benefits, such as low systemic toxicity, minimal invasiveness, and the ability to stimulate antitumor immune responses. For certain types of cancer, it has shown positive results with few side effects. However, PDT still faces some challenges, including limited light penetration into deeper tumor tissues, uneven distribution of the photosensitizer (PS) that can also affect healthy cells, and the difficulties posed by the hypoxic tumor microenvironment (TME). In hypoxic conditions, PDT’s effectiveness is reduced due to insufficient production of reactive oxygen species, which limits tumor destruction and can lead to relapse. This review highlights recent advances in photosensitizers and nanotechnologies that are being developed to improve PDT. It focuses on multifunctional nanoplatforms and nanoshuttles that have shown promise in preclinical studies, especially for treating solid tumors. One of the key areas of focus is the development of PSs that specifically target mitochondria to treat deep-seated malignant tumors. New mitochondria-targeting nano-PSs are designed with better water solubility and extended wavelength ranges, allowing them to target tumors more effectively, even in challenging, hypoxic environments. These advancements in PDT are opening new doors for cancer treatment, especially when combined with other therapeutic strategies. Moving forward, research should focus on optimizing PDT, creating more efficient drug delivery systems, and developing smarter PDT platforms. Ultimately, these efforts aim to make PDT a first-choice treatment option for cancer patients. Full article
(This article belongs to the Special Issue The Roles of Photodynamic Therapy in Tumors and Cancers)
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20 pages, 2090 KiB  
Review
Hybrid Nanoplatforms Based on Photosensitizers and Metal/Covalent Organic Frameworks for Improved Cancer Synergistic Treatment Nano-Delivery Systems
by Aviwe Magadla
Molecules 2025, 30(4), 884; https://doi.org/10.3390/molecules30040884 - 14 Feb 2025
Cited by 2 | Viewed by 1255
Abstract
Researchers have extensively investigated photosensitizer (PS) derivatives for various applications due to their superior photophysical and electrochemical properties. However, inherent problems, such as instability and self-quenching under physiological conditions, limit their biological applications. Metal-organic frameworks (MOFs) and covalent organic frameworks (COFs) represent two [...] Read more.
Researchers have extensively investigated photosensitizer (PS) derivatives for various applications due to their superior photophysical and electrochemical properties. However, inherent problems, such as instability and self-quenching under physiological conditions, limit their biological applications. Metal-organic frameworks (MOFs) and covalent organic frameworks (COFs) represent two relatively new material types. These materials have high surface areas and permanent porosity, and they show a tremendous deal of potential for applications like these. This review summarizes key synthesis processes and highlights recent advancements in integrating PS-based COF and MOF nanocarriers for biomedical applications while addressing potential obstacles and prospects. Full article
(This article belongs to the Special Issue Metal Complexes as Potential Therapeutic Agents)
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12 pages, 3043 KiB  
Article
Analysis of Singlet Oxygen Luminescence Generated By Protoporphyrin IX
by Vikas Vikas, Weibing Yang, Brian C. Wilson, Timothy C. Zhu and Robert H. Hadfield
Antioxidants 2025, 14(2), 176; https://doi.org/10.3390/antiox14020176 - 31 Jan 2025
Cited by 3 | Viewed by 1675
Abstract
The effectiveness of photodynamic therapy (PDT) for cancer treatment relies on the generation of cytotoxic singlet oxygen (1O2) in type II PDT. Hence, monitoring of 1O2 generation during PDT enables optimal treatment delivery to the tumor target [...] Read more.
The effectiveness of photodynamic therapy (PDT) for cancer treatment relies on the generation of cytotoxic singlet oxygen (1O2) in type II PDT. Hence, monitoring of 1O2 generation during PDT enables optimal treatment delivery to the tumor target with reduced off-target effects. Direct 1O2 observation by measuring its luminescence at 1270 nm remains challenging due to the very weak signal. This study presents 1O2 luminescence measurements using a time-resolved singlet oxygen luminescence detection system (TSOLD) applied to protoporphyrin IX (PpIX) in different solvents (ethanol and acetone) and biological media (bovine serum albumin and agarose-based solid phantom). The compact experimental setup includes a nanosecond diode laser with a function generator, a cuvette with photosensitizer solution, optical filtering and mirrors, an InGaAs single-photon avalanche diode detector, and time-tagger electronics. Increasing the concentration of PpIX in these media from 1 to 10 µg/g resulted in a 3–5 × increase in the 1O2 luminescence signal. Furthermore, increasing light scattering in the sample using Intralipid from 0.1 to 1% led to a decrease in the 1O2 luminescence signal and lifetime. These results confirm the marked effect of the microenvironment on the 1O2 signal and, hence, on the photodynamic efficacy. Full article
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