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

OBJECTIVES: The application of photodynamic therapy in solid tumors has attracted increasing attention in recent years, and the efficiency of photosensitizers is a crucial determinant of therapeutic efficacy. This study aims to evaluate the cytotoxic effects of a novel photosensitizer, PEG-MTPABZ-PyC, in photodynamic therapy against gastric cancer cells. METHODS: Gastric cancer MKN45 cells were treated with PEG-MTPABZ-PyC. A high-content live-cell imaging system was used to assess the cellular uptake kinetics and subcellular localization of the photosensitizer. The cytotoxic effects of PEG-MTPABZ-PyC-mediated photodynamic therapy were examined using the cell counting kit-8 (CCK-8) assay and flow cytometry, while the intrinsic cytotoxicity of the photosensitizer alone was verified by the CCK-8 assay. Intracellular reactive oxygen species (ROS) generation after photodynamic therapy was detected using 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA). RESULTS: PEG-MTPABZ-PyC alone exhibited no cytotoxicity toward MKN45 cells, indicating excellent cytocompatibility. The compound efficiently entered cells within 6 hours and localized predominantly in lysosomes. Upon light irradiation, PEG-MTPABZ-PyC-mediated photodynamic therapy induced significant cytotoxicity compared with the control group (P<0.05) and generated abundant intracellular ROS. CONCLUSIONS The novel photosensitizer PEG-MTPABZ-PyC demonstrates potent photodynamic cytotoxicity against gastric cancer cells, showing promising potential for further development in gastric cancer photodynamic therapy.
Humans ; Stomach Neoplasms/drug therapy* ; Photochemotherapy/methods* ; Photosensitizing Agents/pharmacology* ; Cell Line, Tumor ; Polyethylene Glycols/chemistry* ; Reactive Oxygen Species/metabolism* ; Mesoporphyrins/pharmacology*

Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), as certain forms of non-melanoma skin cancer (NMSC) or keratinocyte carcinoma, are the most common forms of malignant neoplasms worldwide (Sharp et al., 2024). BCC and cSCC have been identified as two major components of NMSC, comprising one-third of all malignancies (Burton et al., 2016). Generally speaking, patients with NMSC tend to have relatively favorable survival outcomes, while different histopathological subtypes of NMSC exhibit distinct biological behaviors (Stătescu et al., 2023). Keratinocyte carcinoma, although not considered as deadly as melanoma, tends to metastasize if left untreated (Civantos et al., 2023; Nanz et al., 2024). cSCC can evolve locally, then aggressively metastasize, invade, and even lead to fatal consequences in a subset of patients (Winge et al., 2023). A solid, pigmented, smooth plaque or a hyperkeratotic papule with or without central ulceration and hemorrhage appears to be characteristic of cSCC (Thompson et al., 2016; Zhou et al., 2023). Of note, a rare type of intraepidermal cSCC in situ often appears as a velvety, demarcated, slightly raised erythematous plaque on the genitalia of men (Yamaguchi et al., 2016). Accounting for approximately 16.0% of scalp tumors and with a rising incidence, cSCC is now the second most common NMSC in humans (Verdaguer-Faja et al., 2024). According to the latest statistics, up to 2%‒5% of cSCCs in situ may gradually progress into invasive cSCCs in the final step (Rentroia-Pacheco et al., 2023). Several risk factors for the carcinogenesis and development of cSCC have been identified, including age, accumulative exposure to ultraviolet light radiation A and B, human papillomavirus infection, arsenic ingestion, chronic scarring, xeroderma pigmentosa, a relevant history of ionizing radiation, androgenetic alopecia in males, and immunosuppression therapy (Martinez and Otley, 2001; Welsch et al., 2012; Mortaja and Demehri, 2023).
Humans ; Aminolevulinic Acid/therapeutic use* ; Skin Neoplasms/pathology* ; Photochemotherapy/methods* ; Female ; Carcinoma, Squamous Cell/pathology* ; Middle Aged ; Photosensitizing Agents/therapeutic use* ; Carcinoma, Basal Cell/drug therapy*

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

Fungal perylenequinones have photodynamic activity and are promising photosensitizers for photodynamic therapy (PDT). Here, we investigated the bactericidal and antitumor activities of phleichrome from the fungal perylenequinone family in vitro. Photodynamic bactericidal activity of phleichrome was analyzed by agar-well diffusion method under dark and illuminated conditions. The photodynamic antitumor activity of phleichrome was analyzed in MCF-7, HeLa, SW480, and HepG2 human cancer cell lines using in vitro cytotoxicity assays. Photodynamic bactericidal activities against Gram-negative and Gram-positive bacteria were species-specific. Antitumor activity against all tumor cell lines increased under the illuminated condition. Depending on the results of the analyses, Phleichrome has potential for further drug development related to its antibacterial and antitumor activities.
Cell Line ; Cell Line, Tumor ; Cladosporium* ; Diffusion ; Fungi* ; Gram-Positive Bacteria ; Humans ; In Vitro Techniques ; Methods ; Photochemotherapy ; Photosensitizing Agents

The decision of the appropriate treatment for pancreatic cystic lesions (PCLs) is becoming increasingly important as the number of incidentally found PCLs increases. A range of modalities have been attempted because there has been an increasing demand for minimally invasive treatment for PCLs due to the large burden of a surgical resection. Endoscopic treatment using endoscopic ultrasonography (EUS), a representative of minimally invasive therapy, can be categorized into two types: ablation therapy by the injection of drugs and topical thermal coagulative therapy through the high topical energy. A number of studies reported the feasibility and efficacy of these treatments; the most common is EUS-guided ablation for PCLS with ethanol alone or in combination with anticancer drugs. Although ablation therapies with drug injection have proven safety and feasibility, there is no consensus regarding the actual treatment effects and indications of these modalities. EUS-guided radiofrequency ablation was recently attempted as a representative method of local thermal coagulation, but further studies will be needed because of the lack of evidence of its feasibility and safety. In addition, a range of treatments for malignant tumors rather than PCLs have been attempted, such as EUS-guided photodynamic therapy, EUS-guided neodymium-doped yttrium aluminum garnet laser, and high-intensity focused ultrasound, based on the data from animal experiments. Through further study, endoscopic treatment is expected to become established as a useful treatment modality for PCLs.
Aluminum ; Animal Experimentation ; Catheter Ablation ; Consensus ; Endosonography ; Ethanol ; Methods ; Pancreatic Cyst ; Photochemotherapy ; Ultrasonography ; Yttrium

OBJECTIVETo investigate the effect of photodynamic therapy combined with compound betamethasone in the treatment of hypertrophic scar.

METHODS37 cases of keloid were divided into two groups, 19 cases in the treatment group, 18 cases in the control group. The patients in treatment group were treated with photodynamic therapy combined with compound betamethasone injection therapy. The patients in the control group were treated by compound betamethasone injection. The effect and recurrence rate were compared before and after treatment.

RESULTSThe effective rate was 89.5% in the treatment group, 55. 6% in the control group, showing significant difference between the two groups (P = 0.029) The relapse rate in treatment group was significantly lower than that in the control group (P = 0.047) CONCLUSIONS: Photodynamic therapy combined with compound betamethasone has good effect and safety for the treatment of hypertrophic scar. The combined treatment can reduce the treatment period and side effects

Betamethasone ; therapeutic use ; Case-Control Studies ; Cicatrix, Hypertrophic ; drug therapy ; Combined Modality Therapy ; methods ; Glucocorticoids ; therapeutic use ; Humans ; Photochemotherapy ; methods ; Recurrence

OBJECTIVETo investigate the effect of 8-aminolevulinic acid (ALA) photodynamic therapy (PDT) on the cell proliferation, apoptosis and collagen secretion in keloid fibroblasts and to provide the theoretical base for ALA-PDT treatment of keloids.

METHODSFibroblasts from keloid patients were cultured to the third generation in vitro and incubated in 0, 1, 3, 6, 9 mmol/L of δ-aminolevulinic acid for 3 h in the darkness. Then they were exposed to 635 nm wavelength red light ( 30 J/cm2 ) and continued incubation 24 h after irradiation. CCK-8 assay was used to detect proliferation inhibition rate of fibroblasts. The content of hydroxyproline was measured by colorimetric method. The expression of p-Akt and programmed cell death 4 ( PDCD4) were detected by Western blot.

RESULTSThe inhibition rate of keloid fibroblasts were respectively 0, (8.30 ± 1.01)%, (29.48 ± 3.27)%, (52.01 ± 5.34)%, (79.99 ± 5.85)% with the presence of difference concentrations (0, 1, 3, 6, 9 mmol/L) of ALA. The content of hydroxyproline were respectively (9.540 0 ± 0.352 42), (6.242 5 ± 0.224 85 ), (5.107 5 ± 0.534 88), (3.490 0 ± 0.623 48), (2.945 0 ± 0.514 10) μg/mg. The relative expression of p-Akt were respectively 1, 0.75 ± 0.12, 0.52 ± 0.14, 0.41 ± 0.18, 0.32 ± 0.09. The relative expression of PDCD4 were respectively 1, 1.18 ± 0.19, 1.51 ± 0.22, 0.15 ± 0.30, 2.44 ± 0.22. The difference was statistically significant when compared the group of 1, 3, 6, 9 mmol/L with 0 mmol/L (P < 0.05).

CONCLUSIONSIn concentration within the range of 1-9 mmol/L, ALA could inhibit the proliferation of fibroblasts significantly, promote fibroblasts apoptosis and reduce the content of hydroxyproline in a dose-dependent manner, indicating that 8-aminolevulinic acid photodynamic therapy may be a potential treatment for keloid.

Aminolevulinic Acid ; pharmacology ; Apoptosis ; drug effects ; Cell Culture Techniques ; Cell Proliferation ; drug effects ; Collagen ; secretion ; Fibroblasts ; cytology ; drug effects ; secretion ; Humans ; Keloid ; drug therapy ; pathology ; Light ; Photochemotherapy ; methods ; Photosensitizing Agents ; pharmacology

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

BACKGROUNDPhotodynamic therapy (PDT) has been recommended as a main treatment for idiopathic choroidal neovascularization (I-CNV). But the visual results of PDT were inconsistent and variable, and PDT may bring severe damage to the retinal pigment epithelium and choriocapillaries. In recent years, intravitreal ranibizumab therapy, showing favorable visual outcomes, has developed as an advanced treatment for choroidal neovascularization (CNV). Although both methods have been reported to be effective in treating I-CNV, there is no detailed comparative report between the two methods. This study aimed to compare visual outcomes, retinal and choroidal thickness between intravitreal ranibizumab therapy and PDT in the treatment of I-CNV, and investigate the correlation of visual outcomes with retinal and choroidal thickness in each of the two groups.

METHODSThirty-seven eyes of 37 patients with I-CNV were involved in this study; 19 eyes were treated with intravitreal ranibizumab therapy and 18 eyes were treated with PDT. The best corrected visual acuity (BCVA) was recorded before and at each follow-up visit after treatments (logMAR). Enhanced-depth imaging optical coherence tomography (EDI-OCT) was used to evaluate the retinal structural changes, and to measure central retinal thickness (CRT) and central choroidal thickness (CCT).

RESULTSMean BCVA was 0.64 ± 0.27 in PDT group and 0.69 ± 0.22 in ranibizumab group at baseline (P = 0.55). When compared with the baseline, mean BCVA in PDT group was improved significantly at 3-month after PDT (0.41 ± 0.16, P = 0.002), then changed little (0.42±0.25 at 12-month, P = 0.88). Whereas mean BCVA in Ranibizumab group was improved significantly at each follow-up visit. It improved much more obviously in the first month and then remained stable. The mean BCVA in the ranibizumab group was significantly better at each follow-up visit than that in PDT (P < 0.05). When compared with the baseline, mean CRT in PDT group decreased significantly since 3-month visit, whereas mean CRT in ranibizumab group decreased significantly from 1-month visit. Mean CRT at 1-month and 3-month decreased much more in ranibizumab group than that in PDT group, almost in the same period as BCVA improving. When compared with the baseline, mean CCT did not change significantly at each follow-up visit in each group (P > 0.05). The CCT difference was not statistically significant between the two groups at each same time visit (P > 0.05). Mean BCVA was correlated with CRT, but was not correlated with CCT.

CONCLUSIONSBoth intravitreal ranibizumab therapy and PDT are effective for the treatment of I-CNV. It is obvious that ranibizumab therapy is significantly superior to PDT in improving BCVA and decreasing CRT. CRT decreases much more rapidly in ranibizumab group than in PDT group, simultaneously with visual improvement. CRT reduction has significant correlation with the visual outcomes in the recovery of I-CNV, whereas BCVA prognosis may have no correlation with CCT. CCT is not changed significantly after each of the treatments. Both PDT and ranibizumab therapy may have no significant effect on choroid.

Antibodies, Monoclonal, Humanized ; administration & dosage ; therapeutic use ; Choroidal Neovascularization ; drug therapy ; therapy ; Female ; Humans ; Intravitreal Injections ; Male ; Photochemotherapy ; methods ; Ranibizumab ; Retina ; drug effects ; pathology ; Visual Acuity ; drug effects