Photodynamic Therapy Research Articles

Photodynamic therapy light’: An enhanced treatment protocol for actinic keratoses with minimal pain and optimal clinical outcome by combining laser-assisted low irradiance PDT with shortened daylight PDT

BackgroundBetween 2003 and 2016, 546 patients in our clinic discontinued outpatient treatment for actinic keratoses (AKs) using conventional photodynamic therapy (PDT) because of intolerable pain, thereby necessitating the use of a less painful procedure. Therefore, we developed a novel off-label PDT protocol: ‘PDT light’. MethodsLaser-assisted low irradiance PDT (li-PDT) was performed beginning in 2014. The dosage was gradually lowered to 8-12 J/cm² in 2018, so that we achieved considerable pain reduction while maintaining comparable therapeutic efficacy. A further considerable reduction in pain was achieved from 2018 onwards by combining the advantages of li-PDT with daylight PDT (DLPDT), thereby resulting in 2018 in the new technique ‘PDT light’. Patients with AK Olsen grades 1 or 2 and field cancerization initially received a mild-fractionated CO2 laser pretreatment prior to MAL-incubation (methyl aminolaevulinate, Metvix ®) under occlusion for 1.5-3 h. Then, patients were illuminated on average for 1.02 min with the Aktilite-LED and, after application of an UV-screen on the illuminated area, sent out into daylight for 1 h. ResultsBetween March and November 2019, we successfully treated 152 cases using the enhanced ‘PDT light’ procedure, with 137 cases achieving at follow-up 1 (on average after 8.14 months) good-to-excellent clearance rates (CLA and CLB together 90%) and minimal adverse effects. ConclusionsThe novel ‘PDT light’ protocol proved to be an excellent and nearly painless method with an average visual-analogue scale (VAS) score of 1.19. Additional advantages included reduced illumination time, shorter outpatient stays in the clinic, fewer adverse effects, and better patient compliance than with DLPDT alone.

Development of chitosan-coated iron oxide hybrid composites associated with hexadecafluorozinc phthalocyanine for photodynamic therapy

An iron oxide nanosystem (Fe3O4Nps) encapsulated with chitosan under the adsorption of hexadecafluorozinc phthalocyanine (ZnPcP16) was developed. The synthesis of Fe3O4Nps was carried out through coprecipitation, followed by coating the nanoparticles with chitosan and incorporation with ZnPcP16. To understand and describe the mechanism of action of Fe3O4Nps-Chitosan-ZnPcP16, we use a variety of physicochemical characterization approaches. Electron microscopy results confirmed the monodispersity of the nanoparticles (13.2 ± 2.3 nm). Size distribution and surface charge (zeta potential) were determined by a dynamic light scattering (DLS) analyzer. VSM measurements confirmed its magnetic properties (1.18 emu.g−1). XDR confirmed the crystalline nature of the nanoparticles. UV-visible absorption and fluorescence spectra were used to evaluate the photophysical behavior of ZnPcP16 and Fe3O4Nps-Chitosan-ZnPcP16. These studies have demonstrated good results through synthesizing Fe3O4Nps-Chitosan-ZnPcP16, which could be a promising candidate for applications in photodynamic therapy.

Metal-Phenolic Nanomaterial with Organelle-Level Precision Primes Antitumor Immunity via mtDNA-dependent cGAS-STING Activation.

New generation of nanomaterials with organelle-level precision provide significant promise for targeted attacks on mitochondria, exhibiting remarkable therapeutic potency. Here, we report a novel amphiphilic phenolic polymer (PF) for the mitochondria-targeted photodynamic therapy (PDT), which can trigger excessive mitochondrial DNA (mtDNA) damage by the synergistic action of oxidative stress and furan-mediated DNA cross-linking. Moreover, the phenolic units on PF enable further self-assembly with Mn2+ via metal-phenolic coordination to form metal-phenolic nanomaterial (PFM). We focus on the synergistic activation of the cGAS-STING pathway by Mn2+ and tumor-derived mtDNA in tumor-associated macrophages (TAMs), and subsequently repolarizing M2-like TAMs to M1 phenotype. We highlight that PFM facilitates the cGAS-STING-dependent immunity at the organelle level for potent antitumor efficacy.

Photoactivated Anticancer Activity of Cobalt(III) Complexes with Naturally Occurring Flavonoids Chrysin and Silibinin.

Photoactive metal complexes of bioessential transition metal ions with natural chelators are gaining interest as photocytotoxic agents for cancer photodynamic therapy (PDT). We report six new cobalt(III) complexes with a mixed-ligand formulation [Co(B)2(L)](ClO4)2 (Co1-Co6), where B represents a N,N-donor α-diimine ligand, namely, phenanthroline (phen; Co1, Co2), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq; Co3, Co4), and dipyrido[3,2-a:2',3'-c]phenazine (dppz; Co5, Co6), and L is the monoanionic form of the naturally occurring flavonoids chrysin (chry; Co1, Co3, Co5) and silibinin (sili; Co2, Co4, Co6). Complexes displayed a d-d absorption band within 500-700 nm and exhibited excellent dark and photostability in solution. Cytotoxicity studies indicated significant activity of Co5 and Co6 against cervical (HeLa) and lung (A549) cancer cells under visible light (400-700 nm) irradiation giving low micromolar IC50 values (2.3-3.4 μM, phototoxicity index~15-30). The complexes demonstrated notably low toxicity against normal HPL1D lung epithelial cells. Flow cytometry assay revealed an apoptotic mode of cell damage triggered by the complexes when irradiated. ROS generation assay indicated the involvement of singlet oxygen species in the cell death mechanism when irradiated with light. Overall, complexes Co5 and Co6 with coordinated dipyridophenazine and flavonoid ligands are potential candidates for cancer PDT applications.

Biosynthesis of Natural and Unnatural Perylenequinones for Drug Development.

A wide range of perylenequinones (PQs) with diverse structures and versatile bioactivities have long been isolated, positioning them as highly promising agents for photodynamic therapy (PDT). However, the lack of an efficient and cost-effective method to obtain these compounds and to introduce structural diversity and complexity currently hinders their further research and application. In this concept, we present a comprehensive overview of the advancements in the biosynthetic pathways of natural PQs based on their structural classification, and also summarize recent progress in the biosynthesis of natural PQs and derivatives. These pioneering efforts may pave the way for structure modification and large-scale bioproduction of natural and unnatural PQs through synthetic biology strategies to promote their drug development.

TME-responsive nanoplatform for multimodal imaging-guided synergistic precision therapy of esophageal cancer via inhibiting HIF-1α signal pathway

Esophageal cancer (EC) is the sixth leading cause of cancer-related deaths, and its treatment poses significant challenges. In recent years, photodynamic, photothermal, and chemodynamic therapies have emerged as alternative strategies for tumor intervention. However, limitations such as poor tumor targeting, insufficient microenvironment responsiveness, and unclear mechanisms hinder their application. In this study, we found that hypoxia-inducible factor 1 alpha (HIF-1α) was highly expressed in clinical EC samples, which contributed to tumor malignancy and metastasis. We developed a carbon dots (CDs)-based tumor microenvironment (TME)-responsive nanoplatform, CDs-MnO2-Au-Cet (CMAC), designed for multimodal imaging-guided precision therapy in EC. Both in vitro and in vivo experiments demonstrated that CMAC effectively targeted and imaged EC cells and tissues. CMAC significantly inhibited tumor growth by inducing apoptosis and reducing lung metastasis. Mechanistically, CMAC administration led to a substantial downregulation of HIF-1α and its downstream targets, GLUT1 and MMP9. In summary, we presented a novel nanoplatform for imaging-guided synergistic therapy in EC, which demonstrated excellent anti-tumor growth and metastasis capabilities, along with favorable biocompatibility. This study laid the groundwork for developing innovative theranostic strategies for EC.

Optical trapping of lipid bodies reveals increased cytoplasm viscosity in Candida tropicalis post antimicrobial photodynamic therapy

Abstract Antimicrobial photodynamic therapy (aPDT) is a common treatment for large cell colonies, but its effectiveness is typically assessed through colony-forming unit counting, which lacks microscopic details about cell death. This study monitors the trap stiffness of optically trapped lipid bodies of Candida tropicalis of approximately 1 μm of radius following aPDT treatment. Methylene blue served as the photosensitizer at 10 μM concentration, with a lethal light dose of 60 J cm-². The results revealed a significant increase in viscosity after aPDT treatment. Additionally, image analysis confirmed substantial morphological changes indicative of cell death. These findings demonstrate the potential of optical tweezers as a non-invasive tool for assessing cellular health by providing both functional (viscosity) and morphological data on the response to aPDT.

Effects of aminolevulinic acid photodynamic therapy combined with antibiotics on Mycobacterium abscessus skin infections: an in vitro and in vivo study

BackgroundMycobacterium abscessus skin infections have emerged as a major medical issue. Traditional antibiotic treatments are challenging, prolonged, and often lead to recurrence, creating an urgent need for new therapies. This study investigates the effectiveness of aminolevulinic acid photodynamic therapy (ALA-PDT) combined with antibiotics in treatmenting M. abscessus, using both in vitro and in vivo methods. MethodsWe treated eight patients with M. abscessus skin infections following cosmetic surgery, using ALA-PDT (ALA concentration: 20%; red light: 80J/cm2) combined with oral or intravenous antibiotics,including clarithromycin, moxifloxacin and amikacin, to treat 8 patients with M. abscessus skin infection after medical cosmetic surgery, and assessed the treatment outcomes. Additionally, four bacterial strains (MAB-A1, MAB-A2, MAB-B1, and MAB-B2) isolated from patients were tested in vitro for ALA-PDT efficacy to determine the optimal ALA-PDT dosage. Furthermore, the strains’ single colony morphology, biofilm formation, and genome characteristics of were analyzed to explore the factors influencing ALA-PDT's bactericidal effects. Finally, a combined ALA-PDT and antibiotics sterilization experiment was conducted in vitro. ResultsClinically, ALA-PDT combined with antibiotics showed strong efficacy in treating M. abscessus skin infections, with no recurrence observed during follow-up. In vitro, ALA-PDT effectively killed M. abscessus, although MAB-B1 and MAB-B2 required a higher ALA-PDT dose compared with MAB-A1 and MAB-A2. Compared to MAB-A1 and MAB-A2, MAB-B1 and MAB-B2 exhibited stronger biofilm formation capabilities and bacterial virulence as well as genome mutations primarily affecting fatty acid synthesis and metabolism, potentially explaining their increased ALA-PDT dosage requirement. Notably, the combination of ALA-PDT and antibiotics exerted markedly higher bactericidal effects in vitro compared with antibiotics alone. ConclusionsALA-PDT combined with antibiotics emerged as an effective treatment for M. abscessus skin infections. However, optimal dosage and antibiotic combinations should be tailored to the characteristics of specific clinical strains.

Post-Space Disinfectants With Sodium Hypochlorite and Methylene Blue Loaded in Silver and Quartz Nanoparticles Activated by Photodynamic Therapy. A SEM Analysis.

Post-space disinfectants methylene blue loaded with silver (Ag) and Quartz nanoparticles (NPs) and MB alone activated by photodynamic therapy (PDT) on the survival of Enterococcus faecalis, smear layer (SL) removal efficacy, and extrusion bond strength (EBS) of fiber posts to canal dentin. Hundred mandibular premolars underwent root canal treatment using the rotary ProTaper system. The canals were obturated and post-space was prepared up to a length of 8 mm, maintaining a 5 mm seal. To assess antibacterial efficacy E. faecalis were inoculated in the canal (n = 20). The samples were then randomly allocated into four groups according to the canal disinfectant used to sterilize the canals. Group 1: 2.5% NaOCl+17% EDTA, Group 2: MB-PDT, Group 3: MB@QP-PDT, and Group 4: MB@AgNP-PDT (n = 25). SEM analysis was conducted on five samples from each disinfectant group to assess the removal of the SL. Survival rates were calculated (n = 5 from each group). Glass fiber post (GFP) was cemented to the root dentin of the remaining samples followed by artificial aging. Sectioning of the specimens was performed in all three-thirds of the canals. PBS was assessed followed by failure evaluation. ANOVA and Tukey post hoc test were used to compare the E. faecalis survival rate and PBS of fiber post among different investigated groups. Group 4 (MB@AgNP-PDT) treated canals exhibited the minimum survival rate (0.30 ± 0.04 CFU/mL) of E. faecalis and maximum PBS. However, the highest survival rate and minimum bond strength of GFP were observed in Group 1 (NaOCl+17% EDTA) and Group 2 (MB-PDT) treated teeth respectively. The highest SL removal was recorded in the coronal section of the samples of Group-4 disinfected with MB@AgNP-PDT. The lowest removal of SL was recorded in Group 2 samples sterilized with MB-PDT at apical one-third. Silver nanoparticles when utilized as nano-carriers to enhance the efficiency of MB activated by PDT, have been shown to exhibit the highest antimicrobial potency, improved capacity for SL removal and improved PBS.

Exploring Epidermodysplasia Verruciformis: A Case Report, Treatment Strategies, and Emerging Therapies

Abstract Introduction/Objective Epidermodysplasia verruciformis (EV) is a rare cutaneous disorder with both inherited and acquired forms. Inherited cases involve mutations in genes such as ERV1 and ERV2, crucial for HPV immunity, while acquired cases affect immunocompromised individuals. EV is linked to cutaneous squamous cell carcinoma (SCC), highlighting the need for prompt diagnosis and treatment. Methods/Case Report A 54-year-old HIV-positive man was referred with a persistent, itchy eruption on his forearms despite given ARV regimen, oral retinoids and topical therapies. Physical examination revealed hypopigmentation and hyperkeratotic plaques on both forearms. Histologic examination revealed large cells with blue-gray cytoplasm and perinuclear halo in the upper epidermis, consistent with EV. Although advised for papilloma virus vaccination and planned for a trial of topical cidofovir, the patient was lost to follow-up. Treatment strategies for EV vary depending on lesion severity. Severe keratinized or precancerous lesions typically require surgical removal as the first-line approach. For early-stage EV with few small lesions, 5-FU, cidofovir, glycolic acid, and imiquimod is recommended. Tazarotene 0.5% cream used twice weekly has shown success in resolving lesions within 14 days. Topical imiquimod’s efficacy appears variable. In HIV-positive patients with EV, topical 1% cidofovir showed success in some cases. Systemic and topical retinoids are advised for diffuse lesions, with electrocautery or cryotherapy as options if initial treatments fail. HPV vaccination combined with oral acitretin, topical tretinoin and imiquimod led to lesion flattening. Continuous low-dose isotretinoin achieved prolonged remission of EV, but its efficacy in acquired EV remains unclear. Topical methyl aminolevulinate followed by photodynamic therapy has also shown promise. Results (if a Case Study enter NA) NA Conclusion Since its discovery in the 1970s, Acquired EV has been observed across diverse demographics, including HIV patients and organ transplant recipients. Advanced HPV typing and sequencing techniques aid in predicting SCC risk. Emerging treatments like topical cidofovir and combination therapies show promise, necessitating larger clinical trials for validation.

A Comparison of Traditional Chinese Medicine and Multiple Conventional Therapy in Treating Oral Lichen Planus: A Network Meta-analysis.

To evaluate and compare the efficacy of seven conventional treatments and traditional Chinese medicine (TCM) combined therapies for oral lichen planus. This study employs PubMed, Web of Science, Cochrane Library, and Cnki to collect studies. After evaluating the quality and bias risk, RevMan 5.4.1 and R Gemtc package was utilised with a visual analogue scale and side effects as outcomes, to compare the efficacy of the seven treatments. This study included 20 studies, with a sample size of 1669. Our results suggest that photodynamic therapy and TCM demonstrate the most significant decrease in visual analogue scale and the rank is as follows: photodynamic therapy > TCM > TCM combined with non-hormonal immunosuppressive drugs > TCM combined with glucocorticoids > chloroquine combined with glucocorticoids > non-hormonal immunosuppressive drugs > glucocorticoids. Among them, compared to glucocorticoids, photodynamic therapy (-1.55, 95% CI: (-3.09, -0.02)), TCM (-1.25, 95% CI: (-2.46, -0.06)) significantly outperform in statistics. Moreover, no side effects were reported by the photodynamic therapy treatment. In the comparison with non-hormonal immunosuppressive drugs, the result indicates TCM (-4.17, 95% CI (-8.24, -0.34)), glucocorticoids (-2.78, 95% CI (-5.69, -0.17)) and their combination (-2.83, 95% CI (-5.93, -0.05)) have a significantly lower probability of the appearance of side effects. This study indicates that TCM, from the perspectives of efficacy and the likelihood of side effects, outperforms all other common therapies, besides photodynamic therapy, in treating oral lichen planus.

Bombesin-Targeted Delivery of β-Carboline-Based Ir(III) and Ru(II) Photosensitizers for a Selective Photodynamic Therapy of Prostate Cancer.

Despite advances in Ir(III) and Ru(II) photosensitizers (PSs), their lack of selectivity for cancer cells has hindered their use in photodynamic therapy (PDT). We disclose the synthesis and characterization of two pairs of Ir(III) and Ru(II) polypyridyl complexes bearing two β-carboline ligands (N^N') functionalized with -COOMe (L1) or -COOH (L2), resulting in PSs of formulas [Ir(C^N)2(N^N')]Cl (Ir-Me: C^N = ppy, N^N' = L1; Ir-H: C^N = ppy, N^N' = L2) and [Ru(N^N)2(N^N')](Cl)2 (Ru-Me: N^N = bpy, N^N' = L1; Ru-H: N^N = bpy, N^N' = L2). To enhance their selectivity toward cancer cells, Ir-H and Ru-H were coupled to a bombesin derivative (BN3), resulting in the metallopeptides Ir-BN and Ru-BN. Ir(III) complexes showed higher anticancer activity than their Ru(II) counterparts, particularly upon blue light irradiation, but lacked cancer cell selectivity. In contrast, Ir-BN and Ru-BN exhibited selective photocytoxicity against prostate cancer cells, with a lower effect against nonmalignant fibroblasts. All compounds generated ROS and induced severe mitochondrial toxicity upon photoactivation, leading to apoptosis. Additionally, the ability of Ir-Me to oxidize NADH was demonstrated, suggesting a mechanism for mitochondrial damage. Our findings indicated that the conjugation of metal PSs with BN3 creates efficient PDT agents, achieving selectivity through targeting bombesin receptors and local photoactivation.

Co-Delivery of VEGF siRNA and THPP via Metal-Organic Framework Reverses Cisplatin-Resistant Non-Small Cell Lung Cancer and Inhibits Metastasis through a MUC4 Regulating Mechanism.

Cisplatin resistance significantly impacts the antitumor efficacy of cisplatin chemotherapy and contributes to poor prognosis, including metastasis. In this study, we present the utilization of metal-organic framework (MOF) nanoparticles as the therapeutic component and drug loading scaffold for implementing a ternary combination therapeutic strategy to combat cisplatin-resistant lung cancer and metastasis. Specifically, by engineering MOFs (Cis@MOF-siVEGF) through the self-assembly of THPP as photosensitizer for photodynamic therapy (PDT), along with the incorporation of cisplatin (DDP) and VEGF siRNA (siVEGF), we propose the leverage of photodynamic-induced oxidative damage and gene silencing of the angiogenic factor to reverse cisplatin resistance and sensitize therapeutic potency. Our findings demonstrated that the chemo/photodynamic/antiangiogenic triple combination therapy via Cis@MOF-siVEGF under irradiation effectively inhibits cisplatin-resistant tumor growth and induces abscopal effects. Importantly, molecular mechanistic exploration suggested that MUC4 exerted regulatory effects on governing cancer metastasis, thus representing a potential immunotherapeutic target for cancer intervention. Overall, our study creates a MOFs-based multicomponent delivery platform for complementary therapeutic modules with synergistically enhanced antitumor efficacy and sheds light on potential regulatory mechanisms on cisplatin-resistance cancers.

Dual-Activatable Nano-Immunomodulator for NIR-II Fluorescence Imaging-Guided Precision Cancer Photodynamic Immunotherapy.

Photodynamic immunotherapy which combines photodynamic therapy with immunotherapy has become an important and effective method for the treatment of cancer. However, most cancer photodynamic immunotherapeutic systems are not able to achieve precise release of immunomodulators, resulting in systemic side effects and poor patient outcomes. Herein, a dual-activatable nano-immunomodulator (DIR NP), which both its photodynamic effect and agonist release can be activated under specific stimuli, is reported for precision cancer photodynamic immunotherapy. The DIR NP is self-assembled from an R848-conjugated amphiphilic polymer (mPEG-TK-R848) and a hydrophobic oxidized bovine serum albumin (BSA-SOH)-conjugatable photosensitizer (DIR). DIR NPs may generate a small amount of 1O2 under 808nm laser irradiation, leading to the cleavage of thioketal (TK) moiety and release of R848 and DIR. The released DIR may conjugate with tumor-overexpressed BSA-SOH, improving its photodynamic efficiency and NIR-II fluorescence signal. Such photodynamic efficiency improvement may further enhance the release of cargoes upon irradiation. The activated photodynamic effect induces immunogenic cell death (ICD) to release immune factors and R848 can enhance the maturation of dendritic cells for inhibiting the growth of both primary and distant tumors and eliminating lung metastasis. Therefore, this study provides a dual-activatable intelligent nano-immunomodulator for precise regulation of tumor photodynamic immunotherapy.

Predominant Binding Mode of Palmatine to DNA.

Palmatine is a protoberberine alkaloid, which may produce singlet oxygen under visible light irradiation and binds to DNA. The fact that singlet oxygen activation in palmatine may be triggered by environmental conditions, and in particular its interaction with nucleic acids, makes it a most suitable candidate for photodynamic therapy and DNA-targeted noninvasive anticancer strategies. Despite these remarkable properties, the actual binding mode between palmatine and DNA has not been resolved, yet. Its elucidation has indeed led to contrasting hypotheses. In this contribution, by using long-range molecular dynamic simulations and enhanced sampling approaches, we unequivocally identify that intercalation is the dominant binding mode of palmatine with DNA, from both a thermodynamic and kinetic point of view.

Antimicrobial Photodynamic Therapy Combined with Photobiomodulation Therapy in Teeth with Asymptomatic Apical Periodontitis: A Case Series

Antimicrobial Photodynamic Therapy Combined with Photobiomodulation Therapy in Teeth with Asymptomatic Apical Periodontitis: A Case Series

Elaborated Bio-Heterojunction With Robust Sterilization Effect for Infected Tissue Regeneration via Activating Competent Cell-Like Antibacterial Tactic.

Phototherapy, such as photothermal therapy (PTT) and photodynamic therapy (PDT) has been a powerful strategy to combat bacterial infection. However, the compact cell membranes of pathogenic bacteria, especially drug-resistant bacteria, significantly diminish the efficiency of heat conduction and impede the entrance of reactive oxygen species (ROS) into cells, resulting in unsatisfactory sterilization. Enlightened by the membrane feature of competent bacteria, herein a MXene/CaO2 bio-heterojunction (MC bio-HJ) is elaborated to achieve rapid disinfection and promote infected tissue regeneration through activating competent cell-like antibacterial tactics. The bio-HJ first compels pathogenic bacteria to become a competent cell-like stage through the coordination of Ca2+ and membrane phospholipid, and potentiates the membrane permeability. Assisted by near infrared (NIR) irradiation, the heat and ROS generated from PTT and PDT of bio-HJ easily pass through bacterial membrane and drastically perturb bacterial metabolism, leading to rapid disinfection. More importantly, employing two in vivo infected model of mice, it have corroborated that the MC bio-HJs not only effectively accelerate MRSA-infected cutaneous regeneration, but also considerably boost osseointegration in an infected bone defect after coating on orthopedic implants. As envisaged, this work demonstrates a novel therapeutic tactic with robust antibacterial effect to remedy infected tissue regeneration through activating competent cell-like stage.

Divergent Syntheses of Near-Infrared Light-Activated Molecular Jackhammers for Cancer Cell Eradication.

Aminocyanines incorporating Cy7 and Cy7.5 moieties function as molecular jackhammers (MJH) through vibronic-driven action (VDA). This mechanism, which couples molecular vibrational and electronic modes, results in picosecond-scale concerted stretching of the entire molecule. When cell-associated and activated by near-infrared light, MJH mechanically disrupts cell membranes, causing rapid necrotic cell death. Unlike photodynamic and photothermal therapies, the ultrafast vibrational action of MJH is unhindered by high concentrations of reactive oxygen species scavengers and induces only a minimal temperature increase. Here, the efficient synthesis of a library of MJH is described using a practical approach to access a key intermediate and facilitating the preparation of various Cy7 and Cy7.5 MJH with diverse side chains in moderate to high yields. Photophysical characterization reveals that structural modifications significantly affect molar extinction coefficients and quantum yields while maintaining desirable absorption and emission wavelengths. The most promising compounds, featuring dimethylaminoethyl and dimethylcarbamoyl substitutions, demonstrate up to sevenfold improvement in phototherapeutic index compared to Cy7.5 amine across multiple cancer cell lines. This synthetic strategy provides a valuable platform for developing potent, light-activated therapeutic agents for cancer treatment, with potentially broad applicability across various cancer types.

Choroidal and Choriocapillaris Changes after Photodynamic Therapy and Subthreshold Micropulse Laser Treatment for Central Serous Chorioretinopathy

Background and Objectives: The aim of the present study is to analyze choroidal and choriocapillaris structural and functional changes in eyes affected by Central serous chorioretinopathy after Photodynamic Therapy (PDT) and Subthreshold Micropulse laser (SML) treatment. Materials and Methods: Forty-two eyes of forty-two patients were analyzed in this observational study. Twenty-four patients underwent SML treatment, whereas eighteen patients were treated with PDT. Examinations were performed at baseline and after 3 months of treatment. Main outcome measures were: Best corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), pigment epithelial detachment (PED) presence and maximum height (PEDMH), and choroidal vascularity index (CVI) measured by means of Spectralis HRA + OCT (Heidelberg Engineering, Heidelberg, Germany) Optical coherence tomography (OCT) and choriocapillaris flow voids (CCFV) measured on Optical Coherence Tomography Angiography (OCT-A) platform PLEX Elite 9000 device (Carl Zeiss Meditec Inc., Dublin, CA, USA). Results: Changes in BCVA were registered in both groups over time (p < 0.001). Structural changes in terms of reduced CMT and PED presence were noted in the two groups at follow-up (p < 0.001 and p = 0.001, respectively). Structural and functional choroidal changes were found in the two groups with reduced CCT and CVI over time (p = 0.004 and p = 0.007, respectively), with significant differences between the two groups for CVI parameter (p = 0.001). CCFV increased over time in the PDT group and decreased in the SML group. Conclusions: PDT and SML are effective approaches in CSC eyes and are able to improve structural and functional parameters over time. Choroidal and choriocapillaris parameters are promising biomarkers able to monitor disease course, showing greater impact of PDT on choroid-choriocapillaris complex over time.

Ferroptosis Induction Enhances Photodynamic Therapy Efficacy for OLK.

Oral leukoplakia (OLK) is the most representative oral potentially malignant disorder, with a high risk of malignant transformation and unclear mechanisms of occurrence. Recently, photodynamic therapy (PDT) has exhibited great potential in the treatment of OLK. However, the efficacy of PDT is difficult to predict and varies from person to person. Ferroptosis-related pathways are upregulated in many cancers, and ferroptosis induction is considered to be a potential synergistic strategy for various antitumor therapies, but its role in OLK treatment remains unclear. This study aimed to determine whether ferroptosis induction can enhance the efficacy of PDT in OLK treatment. Our study revealed that solute carrier family 7 member 11 (SLC7A11), a component of a crucial amino acid transporter and a key negative regulator of ferroptosis, was found to be highly expressed in OLK patients with no response to PDT. 5-Aminolevulinic acid (ALA)-PDT is known to cause apoptosis and necrosis, but ferroptosis also occurred under ALA-PDT in OLK cells in our study. Using erastin to induce ferroptosis enhanced the efficacy of ALA-PDT on OLK cells by disrupting the antioxidant system and further elevating intracellular reactive oxygen species levels, leading to increased apoptosis. Furthermore, this combined modality also enhanced the efficacy of ALA-PDT on 4-nitroquinoline-1-oxide (4NQO)-induced OLK lesions in mice. In summary, ferroptosis induction may serve as a potential strategy to enhance the efficacy of ALA-PDT for OLK treatment.