Metal ion-promoted chemodynamic therapy(CDT) combined with photodynamic therapy(PDT) offers broad application prospects for enhancing anti-tumor effects. In this study, glycyrrhizic acid(GA), copper ions(Cu~(2+)), and norcantharidin(NCTD) were co-assembled to successfully prepare a natural small-molecule, carrier-free hydrogel(NCTD Gel) with excellent material properties. Under 808 nm laser irradiation, NCTD Gel responded to the tumor microenvironment(TME) and acted as an efficient Fenton reagent and photosensitizer, catalyzing the conversion of endogenous hydrogen peroxide(H_2O_2) within the tumor into oxygen(O_2), and hydroxyl radicals(·OH, type Ⅰ reactive oxygen species) and singlet oxygen(~1O_2, type Ⅱ reactive oxygen species), while depleting glutathione(GSH) to stabilize reactive oxygen species and alleviate tumor hypoxia. In vitro and in vivo experiments demonstrated that NCTD Gel exhibited significant CDT/PDT synergistic therapeutic effects. Further safety evaluation and metabolic testing confirmed its good biocompatibility and safety. This novel hydrogel is not only simple to prepare, safe, and cost-effective but also holds great potential for clinical transformation, providing insights and references for the research and development of metal ion-mediated hydrogel-based anti-tumor therapies.
Hydrogels/chemistry* ; Animals ; Photochemotherapy ; Humans ; Mice ; Antineoplastic Agents/administration & dosage* ; Photosensitizing Agents/chemistry* ; Neoplasms/metabolism* ; Female ; Copper/chemistry* ; Reactive Oxygen Species/metabolism* ; Tumor Microenvironment/drug effects* ; Cell Line, Tumor ; Male

Research in photodynamic therapy (PDT) primarily focuses on enhancing light penetration depth, improving oxygen supply, and optimizing photosensitizer delivery. Notably, the delivery efficiency of the photosensitizer is crucial for therapeutic efficacy. Carboxyl-substituted phthalocyanines, as important photosensitizing molecules, possess unique chemical modification sites that enable direct targeted delivery or integration into diverse delivery systems. Their synthesis predominantly employs mixed- or cross-condensation, selective synthesis, and axial modification strategies to introduce carboxyl groups. However, their inherent hydrophobicity significantly hinders effective delivery. To address this limitation, modifications with peptides or quaternary ammonium salt derivatives may facilitate precise delivery to tumor cells and pathogens. With advances in nanotechnology, carboxyl-substituted phthalocyanines can serve as key photosensitizer modules, effectively integrated into nanomaterials such as biomacromolecules, inorganic metals, and polymers for both active and passive delivery. Recently, researchers have exploited the π-π stacking and other intermolecular forces among carboxyl-substituted phthalocyanine molecules to drive their self-assembly into nano-micelles, enabling carrier-free delivery or co-delivery with other therapeutic agents for synergistic effects. This review systematically outlines the synthesis strategies for carboxyl-substituted phthalo-cyanines. Taking mono-carboxyl-substituted zinc phthalocyanine as a model molecule, the performance of three delivery modalities were compared: single-molecule targeted delivery, nanocarrier-encapsulated delivery, and carrier-free self-assembled delivery, in terms of PDT efficacy, biocompatibility, and imaging-guided tracing capabilities, to provide a systematic technical framework for the rational design of novel modular photosensitizers and to advance the clinical translation of PDT in precision oncology and anti-infective therapy.
Photochemotherapy/methods* ; Indoles/administration & dosage* ; Isoindoles ; Photosensitizing Agents/administration & dosage* ; Drug Delivery Systems ; Humans

With recent developments in photosensitizers and light delivery systems, topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) has become the fourth alternative therapeutic approach in the management of oral leucoplakia (OLK) due to its minimally invasive nature, efficacy, and low risk of systemic side effects and disfigurement. This report presents step-by-step guidelines for applying topical ALA-PDT in the management of OLK based on both the clinical experience of the authors and a systematic review of the current literature. Studies using protocols with standardized parameters and randomized clinical trials at multiple centres with adequate sample sizes and both interim and long-term follow-ups are needed before universally applicable guidelines can be produced in this field.
Aminolevulinic Acid ; administration & dosage ; therapeutic use ; Humans ; Leukoplakia, Oral ; therapy ; Photochemotherapy ; methods ; Photosensitizing Agents ; administration & dosage ; therapeutic use ; Practice Guidelines as Topic

PURPOSE: To study the retinal pigment epithelium (RPE) and retinal alterations in chronic central serous chorioretinopathy treated with photodynamic therapy, and its correlation with functional parameters such as best-corrected visual acuity (BCVA) and contrast sensitivity (CS). METHODS: Retrospective, noncomparative, consecutive evaluation by optical coherence tomography and its correlation with BCVA and CS in 31 eyes of 26 patients. RESULTS: In all affected patients, 88.5% were male with a mean age of 42.9 years. The right eye was involved in 64.5% of cases, bilateral in 19% and 73.9% were hyperopic (spherical refraction between 0 and +5.0 diopters). Of these cases, 51.5% had peri-RPE abnormalities, 17.3% hyperreflective substances at RPE, 19.4% RPE atrophy, 55.3% foveolar atrophy, 3.1% pigment epithelial detachment, 5.2% subretinal fluid persistence, 8.3% fibrin deposits, 68.4% photoreceptor inner and outer segment line interruption and 31.1% external limiting membrane interruption. CONCLUSIONS: Time evolution and number of outbreaks were related to the decrease in foveal and chorodial thickness and in those with worse BCVA and CS. RPE abnormalities and atrophy were related to the age of onset of symptoms. Photoreceptor elongation has been correlated with poor BCVA and inner and outer segment line destructuring and interruption with poor CS.
Adult ; Central Serous Chorioretinopathy/diagnosis/*drug therapy/physiopathology ; Chronic Disease ; Female ; Fluorescein Angiography ; Follow-Up Studies ; Fundus Oculi ; Humans ; Male ; Middle Aged ; Photochemotherapy/*methods ; Photosensitizing Agents/administration & dosage ; Porphyrins/*administration & dosage ; Retina/*diagnostic imaging/drug effects/physiopathology ; Retrospective Studies ; Tomography, Optical Coherence ; Treatment Outcome ; *Visual Acuity

Cancer, as a serious threat to human health, is one of the major killers. The treatment of cancer has attracted more and more attention. Currently, the means of treating cancer is also increasing, but there is no emergence of a fully satisfactory treatment. A combination of sonodynamic therapy (SDT) and photodynamic therapy (PDT), named sono-photodynamic therapy (S-PDT), is a new composite cancer therapy. Because the therapy can significantly improve the tumor curing effect, it has good application prospects in cancer prevention and treatment. The present article reviewed the progress of the anti-tumor mechanisms and influencing factors of S-PDT.
Animals ; Antineoplastic Agents ; administration & dosage ; Combined Modality Therapy ; Hematoporphyrin Derivative ; administration & dosage ; Hematoporphyrin Photoradiation ; Humans ; Neoplasms ; drug therapy ; therapy ; Photochemotherapy ; methods ; Photosensitizing Agents ; administration & dosage ; Ultrasonic Therapy ; methods

PURPOSE: To evaluate the outcome of a combined photodynamic therapy and intravitreal injection of bevacizumab in choroidal neovascularization secondary to age-related macular degeneration. METHODS: Photodynamic therapy (PDT) was administered to 28 eyes followed by 3 consecutive bevacizumab injections. Patients were followed-up for more than 12 months. At baseline, 1, 3, 6, and 12 months post PDT, visual acuity (VA) and central macular thickness were measured using optical coherence tomography. RESULTS: The mean VA was significantly improved from logarithm of the minimal angle of resolution 0.86 at baseline to 0.69 at 1 month (p = 0.011), 0.63 at 3 months (p = 0.003), 0.64 at 6 months (p = 0.004) and 0.60 at 12 months (p < 0.001). Central macular thickness decreased significantly from 328.3 microm at baseline to 230.0 microm at 6 months and 229.9 microm at 1 year (p < 0.001). Reinjection mean number was 0.4 for 6 months and 0.8 for 12 months. By 1 year, retreatment was performed in 10 eyes (36%). CONCLUSIONS: PDT combined with three consecutive intraviteal bevacizumab injections was effective in improving VA and reducing central macular thickness.
Aged ; Angiogenesis Inhibitors/*administration & dosage ; Antibodies, Monoclonal, Humanized/*administration & dosage ; Choroidal Neovascularization/diagnosis/*drug therapy/etiology ; Dose-Response Relationship, Drug ; Drug Therapy, Combination ; Female ; Fluorescein Angiography ; Follow-Up Studies ; Fundus Oculi ; Humans ; Intravitreal Injections ; Macula Lutea/drug effects/*pathology ; Macular Degeneration/*complications/diagnosis/drug therapy ; Male ; Photochemotherapy/*methods ; Photosensitizing Agents/administration & dosage ; Porphyrins/*administration & dosage ; Retrospective Studies ; Tomography, Optical Coherence ; Treatment Outcome ; Visual Acuity

OBJECTIVE: To observe the effect of the three stages of 5-aminolevulinic acid-photodynamic therapy (ALA-PDT) on condyloma acuminatum of external urethral meatus. METHODS: A total of 56 patients with condyloma acuminatum of external urethral meatus presenting at the Department of Dermatology of Xiangya Hospital from Janunary 2009 to September 2009 were randomly treated by the three stages of ALA-PDT. The topical ALA followed by PDT was carried out once a week for 3 weeks. Rates of cure, ineffectiveness, adverse effects and complications were observed. The follow-up time was 6 months and the recurrence rates were documented. RESULTS: After treatment of three stages of ALA-PDT, complete remission was achieved in 48 out of the 56 patients (85.7%). The recurrence rate was 14.3% (8 cases), and 2 patients had no responses (3.6%). Only 1 patient had serious pain during the treatment, and the rate of adverse effect was 1.8%. No complications were observed. CONCLUSION The three stages of ALA-PDT are safe, effective and tolerant treatment for condyloma acuminatum of external urethral meatus.
Adult ; Aminolevulinic Acid ; administration & dosage ; Condylomata Acuminata ; drug therapy ; Humans ; Male ; Photochemotherapy ; Photosensitizing Agents ; administration & dosage ; Urethral Diseases ; drug therapy

Targeted drug delivery can significantly increase the concentration of the drug in treatment site, and decrease the dosage of drugs, cost of treatment and the drug's adverse effects on the body. So targeted drug delivery is the hotspot of recent studies. This paper reviews the development of targeted drug delivery research in recent years, including three areas: passive targeting, active targeting, and physical and chemical targeting.
Animals ; Antibodies ; metabolism ; Drug Carriers ; Drug Delivery Systems ; methods ; trends ; Emulsions ; Humans ; Liposomes ; Magnetics ; Microspheres ; Nanoparticles ; Pharmaceutical Preparations ; administration & dosage ; Photosensitizing Agents ; pharmacology ; Prodrugs ; Receptors, Cell Surface ; metabolism

This investigation was made with regard to the influences of ultrasound combined with hematoporphyrin on the activities of antioxidative enzyme in ascites hepatoma 22 (H-22) tumor cells, and to a better understanding of the potential biological mechanism of sonodynamic therapy which involved the damage to cells. Combined with 100 microg/ml hematoporphyrin, high intensity focused ultrasound sonication at a frequency of 1.43 MHz and an intensity level of 2.0 W/cm2 was delivered to H-22 tumor cells for 1 min. The viability of cells was evaluated by typan-blue blue exclusion test. The intracellular reactive oxygen species (ROS) levels were determined by 2',7'-dichlorofluorescein diacetata (DCFH-DA). Enzymatic chemical methods were used to measure the activities of key antioxidative enzymes. The results indicated that the cell damage rate of ultrasound combined with hematoporphyrin was significantly higher than that of the treatment with ultrasound alone, and hematoporphyrin alone had no killing effect on H-22 cells. The level of ROS in cell suspension was significantly increased, and the key antioxidative enzyme activities were obviously decreased after treatment with the combined use of ultrasound and hematoporphyrin. We speculated that the decreased activities of key antioxidative enzymes in cells might be involved in mediating the killing effect on H22 cells in sonodynamic therapy.
Animals ; Female ; Glutathione Peroxidase ; metabolism ; Hematoporphyrins ; administration & dosage ; radiation effects ; Liver Neoplasms, Experimental ; enzymology ; therapy ; Mice ; Mice, Inbred ICR ; Photochemotherapy ; methods ; Photosensitizing Agents ; administration & dosage ; radiation effects ; Superoxide Dismutase ; metabolism ; Ultrasonics

PURPOSE: To report a case of retinal capillary hemangioma treated with verteporfin photodynamic therapy combined with intravitreal triamcinolone acetonide. METHODS: A 15-year-old female presented with metamorphopsia in the left eye for 7 days. Examination showed peripheral endophytic retinal capillary hemangioma, macular edema, and a best-corrected visual acuity of 20/50. The hemangioma and macular edema were treated with verteporfin photodynamic therapy and intravitreal triamcinolone acetonide. RESULTS: After 5 months of follow-up, involution of the hemangioma, reduction of macular edema, decrease of the feeder and draining vessel diameter, and improvement of best-corrected visual acuity to 20/25 was seen. CONCLUSIONS: This verteporfin photodynamic therapy combined with intravitreal triamcinolone acetonide appeared to cause involution of the hemangioma with reduction in macular edema and improvement in visual acuity.
Adolescent ; Female ; Fundus Oculi ; Glucocorticoids/*administration & dosage/therapeutic use ; Hemangioma, Capillary/diagnosis/*drug therapy ; Humans ; Injections ; *Photochemotherapy ; Photosensitizing Agents/*therapeutic use ; Porphyrins/*therapeutic use ; Retinal Neoplasms/diagnosis/*drug therapy ; Tomography, Optical Coherence ; Triamcinolone Acetonide/*administration & dosage/therapeutic use ; Ultrasonography ; Vitreous Body