Automatic segmentation of lysosomes and analysis of intracellular pH with Radachlorin photosensitizer and FLIM.

We report application of the fluorescence lifetime imaging microscopy (FLIM) for analysis of distributions of intracellular acidity using a chlorin-e6 based photosensitizer Radachlorin. An almost two-fold increase of the photosensitizer fluorescence lifetime in alkaline microenvironments as compared to acidic ones allowed for clear distinguishing between acidic and alkaline intracellular structures. Clusterization of a phasor plot calculated from fits of the FLIM raw data by two Gaussian distributions provided accurate automatic segmentation of lysosomes featuring acidic contents. The approach was validated in colocalization experiments with LysoTracker fluorescence in living cells of four established lines. The dependence of photosensitizer fluorescence lifetime on microenvironment acidity allowed for estimation of pH inside the cells, except for the nuclei, where photosensitizer does not penetrate. The developed method is promising for combined application of the photosensitizer for both photodynamic treatment and diagnostics.

Comparative analysis of whole cell-derived vesicular delivery systems for photodynamic therapy of extrahepatic cholangiocarcinoma.

This first-in-its-class proof-of-concept study explored the use of bionanovesicles for the delivery of photosensitizer into cultured cholangiocarcinoma cells and subsequent treatment by photodynamic therapy (PDT). Two types of bionanovesicles were prepared: cellular vesicles (CVs) were fabricated by sonication-mediated nanosizing of cholangiocarcinoma (TFK-1) cells, whereas cell membrane vesicles (CMVs) were produced by TFK-1 cell and organelle membrane isolation and subsequent nanovesicularization by sonication. The bionanovesicles were loaded with zinc phthalocyanine (ZnPC). The CVs and CMVs were characterized (size, polydispersity index, zeta potential, stability, ZnPC encapsulation efficiency, spectral properties) and assayed for tumor (TFK-1) cell association and uptake (flow cytometry, confocal microscopy), intracellular ZnPC distribution (confocal microscopy), dark toxicity (MTS assay), and PDT efficacy (MTS assay). The mean ±â€¯SD diameter, polydispersity index, and zeta potential were 134 ±â€¯1 nm, -16.1 ±â€¯0.9, and 0.220 ±â€¯0.013, respectively, for CVs and 172 ±â€¯3 nm, -16.4 ±â€¯1.1, and 0.167 ±â€¯0.022, respectively, for CMVs. Cold storage for 1 wk and incorporation of ZnPC increased bionanovesicular diameter slightly but size remained within the recommended range for in vivo application (136-220 nm). ZnPC was incorporated into CVs and CMVs at an optimal photosensitizer:lipid molar ratio of 0.006 and 0.01, respectively. Both bionanovesicles were avidly taken up by TFK-1 cells, resulting in homogenous intracellular ZnPC dispersion. Photosensitization of TFK-1 cells did not cause dark toxicity, while illumination at 671 nm (35.3 J/cm2) produced LC50 values of 1.11 µM (CVs) and 0.51 µM (CMVs) at 24 h post-PDT, which is superior to most LC50 values generated in tumor cells photosensitized with liposomal ZnPC. In conclusion, CVs and CMVs constitute a potent photosensitizer platform with no inherent cytotoxicity and high PDT efficacy in vitro.

Giant retinal pigment epithelial tear following photodynamic therapy for the bullous variant of central serous chorioretinopathy: A case report.

RATIONALE: The bullous variant of central serous chorioretinopathy (CSC) is a severe form of chronic CSC. Patients with the bullous variant of CSC have an increased risk of experiencing multiple pigment epithelial detachments (PEDs) and retinal pigment epithelium (RPE) tears. Photodynamic therapy (PDT) is a treatment for the bullous variant of CSC. RPE tear is a possible postoperative complication of PDT for eyes with PEDs. To our knowledge, no cases of giant RPE tears following PDT for the bullous variant of CSC have been reported previously. This case report presents the first instance of a giant RPE tear after half-time PDT for the bullous variant of CSC, accompanied by a series of images depicting the tear development. PATIENT CONCERNS: A 63-year-old male patient presented with rapidly deteriorating vision in his left eye over a 3-month period. He also reported a previous episode of vision loss in his right eye 2 years prior. Best-corrected visual acuity (BCVA) in the left eye was 0.2. DIAGNOSIS: The right eye was diagnosed with chronic non-bullous CSC, while the left eye was diagnosed with the bullous variant of CSC with a large PED. INTERVENTIONS: Half-time PDT was administered to the left eye. OUTCOMES: One month after half-time PDT, a giant RPE tear exceeding 3 clock-hours in size was confirmed in the lower temporal quadrant of the left eye. Three months after the initial half-time PDT, a second half-time PDT was performed owing to recurrent retinal detachment. Two months after the second half-time PDT, the retinal detachment resolved, and BCVA improved to 0.4, 6 months after the second half-time PDT. LESSONS: In cases where the bullous variant of CSC is complicated by extensive PED, clinicians should consider the potential development of a giant RPE tear as a treatment complication.

Targeted Ultrasound Nanobubbles Therapy for Prostate Cancer via Immuno-Sonodynamic Effect.

Background: Prostate cancer (PCa) poses a significant global health threaten. Immunotherapy has emerged as a novel strategy to augment the inhibition of tumor proliferation. However, the sole use of anti-PD-L1 Ab for PCa has not yielded improvements, mirroring outcomes observed in other tumor types. Methods: This study employed the thin film hydration method to develop lipid nanobubbles (NBs) encapsulating chlorin e6 (Ce6) and anti-PD-L1 Ab (Ce6@aPD-L1 NBs). Our experimental approach included cellular assays and mouse immunization, providing a comprehensive evaluation of Ce6@aPD-L1 NBs' impact. Results: The Ce6@aPD-L1 NBs effectively induced reactive oxygen species generation, leading to tumor cells death. In mice, they demonstrated a remarkable enhancement of immune responses compared to control groups. These immune responses encompassed immunogenic cell death induced by sonodynamic therapy and PD-1/PD-L1 blockade, activating dendritic cells maturation and effectively stimulating CD8+T cells. Conclusion: Ce6@aPD-L1 NBs facilitate tumor-targeted delivery, activating anti-tumor effects through direct sonodynamic therapy action and immune system reactivation in the tumor microenvironment. Ce6@aPD-L1 NBs exhibit substantial potential for achieving synergistic anti-cancer effects in PCa.

Effect of photodynamic therapy with 5-aminolevulinic acid and EDTA-2Na against mixed infection of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa.

BACKGROUND: The increasing abundance of drug-resistant bacteria is a global threat. Photodynamic therapy is an entirely new, non-invasive method for treating infections caused by antibiotic-resistant strains. We previously described the bactericidal effect of photodynamic therapy on infections caused by a single type of bacterium. We showed that gram-positive and gram-negative bacteria could be killed with 5-aminolevulic acid and 410 nm light, respectively. However, clinically, mixed infections are common and difficult to treat. OBJECTIVE: We investigated the bactericidal effects of photodynamic therapy on mixed infections of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. METHODS: We compared bacterial growth with and without photodynamic therapy in vitro. Then, in vivo, we studied mixed infections in a mouse skin ulcer model. We evaluated the rates of ulcer area reduction and transitions to healing in treated and untreated mice. In addition, a comparison was made between PDT and existing topical drugs. RESULTS: We found that photodynamic therapy markedly reduced the growth of both methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, in culture, and it reduced the skin ulcer areas in mice. PDT was also more effective than existing topical medicines. CONCLUSION: This study showed that photodynamic therapy had antibacterial effects against a mixed infection of gram-positive and gram-negative bacteria, and it promoted skin ulcer healing. These results suggested that photodynamic therapy could be effective in both single- and mixed-bacterial infections.

Tumor microenvironment activated mussel-inspired hollow mesoporous nanotheranostic for enhanced synergistic photodynamic/chemodynamic therapy.

Anti-tumor therapies reliant on reactive oxygen species (ROS) as primary therapeutic agents face challenges due to a limited oxygen substrate. Photodynamic therapy (PDT) is particularly hindered by inherent hypoxia, while chemodynamic therapy (CDT) encounters obstacles from insufficient endogenous hydrogen peroxide (H2O2) levels. In this study, we engineered biodegradable tumor microenvironment (TME)-activated hollow mesoporous MnO2-based nanotheranostic agents, designated as HAMnO2A. This construct entails loading artemisinin (ART) into the cavity and surface modification with a mussel-inspired polymer ligand, namely hyaluronic acid-linked poly(ethylene glycol)-diethylenetriamine-conjugated (3,4-dihydroxyphenyl) acetic acid, and the photosensitizer Chlorin e6 (mPEG-HA-Dien-(Dhpa/Ce6)), facilitating dual-modal imaging-guided PDT/CDT synergistic therapy. In vitro experimentation revealed that HAMnO2A exhibited ideal physiological stability and enhanced cellular uptake capability via CD44-mediated endocytosis. Additionally, it was demonstrated that accelerated endo-lysosomal escape through the pH-dependent protonation of Dien. Within the acidic and highly glutathione (GSH)-rich TME, the active component of HAMnO2A, MnO2, underwent decomposition, liberating oxygen and releasing both Mn2+ and ART. This process alleviates hypoxia within the tumor region and initiates a Fenton-like reaction through the combination of ART and Mn2+, thereby enhancing the effectiveness of PDT and CDT by generating increased singlet oxygen (1O2) and hydroxyl radicals (•OH). Moreover, the presence of Mn2+ ions enabled the activation of T1-weighted magnetic resonance imaging. In vivo findings further validated that HAMnO2A displayed meaningful tumor-targeting capabilities, prolonged circulation time in the bloodstream, and outstanding efficacy in restraining tumor growth while inducing minimal damage to normal tissues. Hence, this nanoplatform serves as an efficient all-in-one solution by facilitating the integration of multiple functions, ultimately enhancing the effectiveness of tumor theranostics.

Iridium(III) complexes decorated with silicane-modified rhodamine: near-infrared light-initiated photosensitizers for efficient deep-tissue penetration photodynamic therapy.

Meeting the demand for efficient photosensitizers in photodynamic therapy (PDT), a series of iridium(III) complexes decorated with silicane-modified rhodamine (Si-rhodamine) was meticulously designed and synthesized. These complexes demonstrate exceptional PDT potential owing to their strong absorption in the near-infrared (NIR) spectrum, particularly responsive to 808 nm laser stimulation. This feature is pivotal, enabling deep-penetration laser excitation and overcoming depth-related challenges in clinical PDT applications. The molecular structures of these complexes allow for reliable tuning of singlet oxygen generation with NIR excitation, through modification of the cyclometalating ligand. Notably, one of the complexes (4) exhibits a remarkable ROS quantum yield of 0.69. In vivo results underscore the efficacy of 4, showcasing significant tumor regression at depths of up to 8.4 mm. This study introduces a promising paradigm for designing photosensitizers capable of harnessing NIR light effectively for deep PDT applications.

Improved effectiveness of X-PDT against human triple-negative breast cancer cells through the use of liposomes co-loaded with protoporphyrin IX and perfluorooctyl bromide.

In this study, we utilized X-ray-induced photodynamic therapy (X-PDT) against triple-negative breast cancer (TNBC) cells. To achieve this, we developed a liposome delivery system that co-loaded protoporphyrin IX (PPIX) and perfluorooctyl bromide (PFOB) in a rational manner. Low-dose X-ray at 2 Gy was employed to activate PPIX for the generation of reactive oxygen species (ROS), and the co-loading of PFOB provided additional oxygen to enhance ROS production. The resulting highly toxic ROS effectively induced cell death in TNBC. In vitro X-PDT effects, including intracellular ROS generation, cell viability, and apoptosis/necrosis assays in TNBC cells, were thoroughly investigated. Our results indicate that the nanocarriers effectively induced X-PDT effects with very low-dose radiation, making it feasible to damage cancer cells. This suggests the potential for the effective utilization of X-PDT in treating hypoxic cancers, including TNBC, with only a fraction of conventional radiotherapy.

ROS-Responsive Bola-Lipid Nanoparticles as a Codelivery System for Gene/Photodynamic Combination Therapy.

The nonviral delivery systems that combine genes with photosensitizers for multimodal tumor gene/photodynamic therapy (PDT) have attracted much attention. In this study, a series of ROS-sensitive cationic bola-lipids were applied for the gene/photosensitizer codelivery. Zn-DPA was introduced as a cationic headgroup to enhance DNA binding, while the hydrophobic linking chains may facilitate the formation of lipid nanoparticles (LNP) and the encapsulation of photosensitizer Ce6. The length of the hydrophobic chain played an important role in the gene transfection process, and 14-TDZn containing the longest chains showed better DNA condensation, gene transfection, and cellular uptake. 14-TDZn LNPs could well load photosensitizer Ce6 to form 14-TDC without a loss of gene delivery efficiency. 14-TDC was used for codelivery of p53 and Ce6 to achieve enhanced therapeutic effects on the tumor cell proliferation inhibition and apoptosis. Results showed that the codelivery system was more effective in the inhibition of tumor cell proliferation than individual p53 or Ce6 monotherapy. Mechanism studies showed that the production of ROS after Ce6 irradiation could increase the accumulation of p53 protein in tumor cells, thereby promoting caspase-3 activation and inducing apoptosis, indicating some synergistic effect. These results demonstrated that 14-TDC may serve as a promising nanocarrier for gene/PDT combination therapy.

Two-Photon Absorbing Dendrimers and Their Properties-An Overview.

This review describes the two-photon absorption properties of dendrimers, which are arborescent three-dimensional macromolecules differing from polymers by their perfectly defined structure. The two-photon absorption process is a third order non-linear optical property that is attractive because it can be used in a wide range of applications. In this review, dendrimers that were studied for their two-photon absorption properties are first described. Then, the use of dendritic TPA chromophores for light harvesting, photopolymerization, optical power limitation, cell imaging, singlet oxygen generation, and photodynamic therapy is described. This review thus proposes an overview of the properties and possible applications of two-photon absorbing dendrimers.

Application of Photodynamic Therapy in Cardiology.

The origins of photodynamic therapy (PDT) date back to 1904. Since then, the amount of research proving PDT and, consequently, its applicability to various disease states has steadily increased. Currently, PDT is mainly used in oncology to destroy cancer cells. It is being worked on for possible use in other medical fields as well, including cardiology. It can be used in the prevention of restenosis, often occurring after vascular surgical interventions, for destroying atherosclerotic plaques and as a new ablative method of ectopic centers in the treatment of atrial fibrillation. The purpose of this review is to summarize the knowledge to date regarding the therapeutic potential of using PDT for various pathological conditions in cardiology. The review also focuses on the current limitations associated with the use of PDT and identifies areas where more research is needed to develop better drug regimens. Materials and methods: The study analyzed 189 medical articles. The articles came from PubMed, Frontiers, Google Scholar, Science Direct and Web of Science databases. Through the excitation of light, a photosensitizer (PS) introduced into the body, the destruction of pathological cells occurs. PTD is widely used in oncology of the central nervous system (CNS). This process is made possible by the production of free oxygen radicals (ROS) and singlet oxygen, which generate oxidative stress that destroys sensitive cancer cells. In recent years, photosensitizers have also been discovered to have a strong affinity for macrophages that fill atherosclerotic plaques, making these compounds suitable for treating atherosclerosis. By inducing apoptosis of smooth muscle cells, inactivating basic fibroblast growth factor (FGF-ß) and inhibiting endothelial cell hyperplasia, PDT can be used to prevent restenosis after surgical proceduresPDT appears to be a minimally invasive and highly effective therapeutic method, especially when combined with other therapeutic methods. Unfortunately, the small number of animal model studies and human clinical trials greatly limit the applicability of PDT on a wider scale. Current limitations, such as the depth of penetration, delivery of photosensitizer particles to the direct site of the lesion or the appropriate choice of photosensitizer in relation to the nature of the pathology, unfortunately make it impossible to replace current therapeutic approaches.

Polydopamine-Coated Liposomes for Methylene Blue Delivery in Anticancer Photodynamic Therapy: Effects in 2D and 3D Cellular Models.

Photodynamic therapy (PDT) is a therapeutic option for cancer, in which photosensitizer (PS) drugs, light, and molecular oxygen generate reactive oxygen species (ROS) and induce cell death. First- and second-generation PSs presented with problems that hindered their efficacy, including low solubility. Thus, second-generation PSs loaded into nanocarriers were produced to enhance their cellular uptake and therapeutic efficacy. Among other compounds investigated, the dye methylene blue (MB) showed potential as a PS, and its photodynamic activity in tumor cells was reported even in its nanocarrier-delivered form, including liposomes. Here, we prepared polydopamine (PDA)-coated liposomes and efficiently adsorbed MB onto their surface. lipoPDA@MB vesicles were first physico-chemically characterized and studies on their light stability and on the in vitro release of MB were performed. Photodynamic effects were then assessed on a panel of 2D- and 3D-cultured cancer cell lines, comparing the results with those obtained using free MB. lipoPDA@MB uptake, type of cell death induced, and ability to generate ROS were also investigated. Our results show that lipoPDA@MB possesses higher photodynamic potency compared to MB in both 2D and 3D cell models, probably thanks to its higher uptake, ROS production, and apoptotic cell death induction. Therefore, lipoPDA@MB appears as an efficient drug delivery system for MB-based PDT.

Efficacy of photodynamic therapy using ALAHCl in gel with a lipid nanoemulsion and MALHCl in cream in superficial basal cell carcinoma.

INTRODUCTION AND OBJECTIVE: Photodynamic therapy (PDT) is a therapeutic option for low-risk basal cell carcinoma (BCC). The aim of the study was to assess the efficacy of topical PDT in the treatment of superficial BCC (sBCC) using two different photosensitizers: aminolevulinic acid hydrochloride (ALA-HCl) in a gel formulation with a lipid nanoemulsion (ALA-HCl in gel) and ALA methyl ester hydrochloride (MAL-HCl) in a cream formulation (MAL-HCl in cream). MATERIAL AND METHODS: 21 patients were treated twice with a one week interval between treatments. The formulations were applied onto lesions: 10 patients were treated with MAL-HCl in cream, and 11 with ALA-HCl in gel. After three hours of incubation and removing the preparations, fluorescence was assessed. The skin areas were then irradiated with red light 630 ± 5 nm. RESULTS: At the follow-up visit 12 weeks after the second treatment, complete clinical remission was found in 82% after ALA-HCl in gel and in 80% after MAL-HCl in cream. An excellent cosmetic result was found in 96% of patients after MALHCl in cream and in 100% after ALA-HCl in gel. Faster skin healing and less post-inflammatory hyperpigmentation during follow-up visits was observed after treatment with ALA-HCl in gel. CONCLUSIONS: Both formulations - ALA-HCl in gel and MAL-HCl in cream - were highly effective photosensitisers for PDT. The advantage of ALA-HCl in a gel formulation with a lipid nanoemulsion was faster skin healing, resulting in better cosmetic results.

Current clinical evidence is insufficient to support HMME-PDT as the first choice of treatment for young children with port wine birthmarks.

BACKGROUND: Port wine birthmark (PWB) is a congenital vascular malformation of the skin. Pulsed dye laser (PDL) is the "gold standard" for the treatment of PWB globally. Hematoporphyrin monomethyl ether (HMME or hemoporfin)-mediated photodynamic therapy (HMME-PDT) has emerged as the first choice for PWB treatment, particularly for young children, in many major hospitals in China during the past several decades. AIM: To evaluate whether HMME-PDT is superior to PDL by comparing the clinical efficacies of both modalities. METHOD: PubMed records were searched for all relevant studies of PWB treatment using PDL (1988-2023) or HMME-PDT (2007-2023). Patient characteristics and clinical efficacies were extracted. Studies with a quartile percentage clearance or similar scale were included. A mean color clearance index (CI) per study was calculated and compared among groups. An overall CI (C0), with data weighted by cohort size, was used to evaluate the final efficacy for each modality. RESULT: A total of 18 HMME-PDT studies with 3910 patients in China were eligible for inclusion in this analysis. Similarly, 40 PDL studies with 5094 patients from nine different countries were eligible for inclusion in this analysis. Over 58% of patients in the HMME-PDT studies were minors (<18 years old). A significant portion (21.3%) were young children (<3 years old). Similarly, 33.2% of patients in the PDL studies were minors. A small proportion (9.3%) was young children. The overall clearance rates for PDL were slightly, but not significantly, higher than those for HMME-PDT in cohorts with patients of all ages (C0, 0.54 vs. 0.48, p = 0.733), subpopulations with only minors (C0, 0.54 vs. 0.46, p = 0.714), and young children (C0, 0.67 vs. 0.50, p = 0.081). Regrettably, there was a lack of long-term data on follow-up evaluations for efficacy and impact of HMME-PDT on young children in general, and central nervous system development in particular, because their blood-brain barriers have a greater permeability as compared to adults. CONCLUSION: PDL shows overall albeit insignificantly higher clearance rates than HMME-PDT in patients of all ages; particularly statistical significance is nearly achieved in young children. Collectively, current evidence is insufficient to support HMME-PDT as the first choice of treatment of PWBs in young children given: (1) overall inferior efficacy as compared to PDL; (2) risk of off-target exposure to meningeal vasculature during the procedure; (3) administration of steriods for mitigation of side effects; -and (4) lack of long-term data on the potential impact of HMME on central nervous system development in young children.

Mitoxantrone encapsulated photosensitizer nanomicelle as carrier-free theranostic nanomedicine for near-infrared fluorescence imaging-guided chemo-photodynamic combination therapy on cancer.

Combination therapy exhibits higher efficacy than any single therapy, inspiring various nanocarrier-assisted multi-drug co-delivery systems for the combined treatment of cancer. However, most nanocarriers are inert and non-therapeutic and have potential side effects. Herein, an amphiphilic polymer composed of a hydrophobic photosensitizer and hydrophilic poly(ethylene glycol) was employed as the nanocarriers and photosensitizers to encapsulate the chemotherapeutic drug mitoxantrone for chemo-photodynamic combination therapy. The resulting nanodrug consisted solely of pharmacologically active ingredients, thus avoiding potential toxicity induced by inert excipients. This multifunctional nanoplatform demonstrated significantly superior treatment performance compared to monotherapy for colorectal cancer, both in vitro and in vivo, achieving near-infrared fluorescence imaging-mediated chemo-photodynamic combined eradication of malignancy.

Gold nanoparticles-mediated photothermal and photodynamic therapies for cancer.

Cancer remains one of the major causes of death globally, with one out of every six deaths attributed to the disease. The impact of cancer is felt on psychological, physical, and financial levels, affecting individuals, communities, and healthcare institutions. Conventional cancer treatments have many challenges and inadequacies. Nanomedicine, however, presents a promising solution by not only overcoming these problems but also offering the advantage of combined therapy for treatment-resistant cancers. Nanoparticles specifically engineered for use in nanomedicine can be efficiently targeted to cancer cells through a combination of active and passive techniques, leading to superior tumor-specific accumulation, enhanced drug availability, and reduced systemic toxicity. Among various nanoparticle formulations designed for cancer treatment, gold nanoparticles have gained prominence in the field of nanomedicine due to their photothermal, photodynamic, and immunologic effects without the need for photosensitizers or immunotherapeutic agents. To date, there is no comprehensive literature review that focuses on the photothermal, photodynamic, and immunologic effects of gold nanoparticles. In this review, significant attention has been devoted to examining the parameters pertaining to the structure of gold nanoparticles and laser characteristics, which play a crucial role in influencing the efficacy of photothermal therapy (PTT) and photodynamic therapy (PDT). Moreover, this article provides insights into the success of PTT and PDT mediated by gold nanoparticles in primary cancer treatment, as well as the immunological effects of PTT and PDT on metastasis and recurrence, providing a promising strategy for cancer therapy. In summary, gold nanoparticles, with their unique properties, have the potential for clinical application in various cancer therapies, including the treatment of primary cancer, recurrence and metastasis.

Targeted Delivery of Catalase and Photosensitizer Ce6 by a Tumor-Specific Aptamer Is Effective against Bladder Cancer In Vivo.

Photodynamic therapy (PDT) is often applied in a clinical setting to treat bladder cancer. However, current photosensitizers report drawbacks such as low efficacy, low selectivity, and numerous side effects, which have limited the clinical values of PDT for bladder cancer. Previously, we developed the first bladder cancer-specific aptamer that can selectively bind to and be internalized by bladder tumor cells versus normal uroepithelium cells. Here, we use an aptamer-based drug delivery system to deliver photosensitizer chlorine e6 (Ce6) into bladder tumor cells. In addition to Ce6, we also incorporate catalase into the drug complex to increase local oxygen levels in the tumor tissue. Compared with free Ce6, an aptamer-guided DNA nanotrain (NT) loaded with Ce6 and catalase (NT-Catalase-Ce6) can specifically recognize bladder cancer cells, produce oxygen locally, induce ROS in tumor cells, and cause mitochondrial apoptosis. In an orthotopic mouse model of bladder cancer, the intravesical instillation of NT-Catalase-Ce6 exhibits faster drug internalization and a longer drug retention time in tumor tissue compared with that in normal urothelium. Moreover, our modified PDT significantly inhibits tumor growth with fewer side effects such as cystitis than free Ce6. This aptamer-based photosensitizer delivery system can therefore improve the selectivity and efficacy and reduce the side effects of PDT treatment in mouse models of bladder cancer, bearing a great translational value for bladder cancer intravesical therapy.

Photodynamic Therapy and Cardiovascular Diseases.

Cardiovascular diseases are the third most common cause of death in the world. The most common are heart attacks and stroke. Cardiovascular diseases are a global problem monitored by many centers, including the World Health Organization (WHO). Atherosclerosis is one aspect that significantly influences the development and management of cardiovascular diseases. Photodynamic therapy (PDT) is one of the therapeutic methods used for various types of inflammatory, cancerous and non-cancer diseases. Currently, it is not practiced very often in the field of cardiology. It is most often practiced and tested experimentally under in vitro experimental conditions. In clinical practice, the use of PDT is still rare. The aim of this review was to characterize the effectiveness of PDT in the treatment of cardiovascular diseases. Additionally, the most frequently used photosensitizers in cardiology are summarized.

Ce6-modified Fe ions-doped carbon dots as multifunctional nanoplatform for ferroptosis and photodynamic synergistic therapy of melanoma.

BACKGROUND: Despite the higher sensitivity of melanoma towards ferroptosis and photodynamic therapy (PDT), the lack of efficient ferroptosis inducers and the poor solubility of photosensitizers restrict their synergistic strategies. With unique advantages, carbon dots (CDs) are expected to serve as innovative building blocks for combination therapy of cancers. RESULTS: Herein, an ferroptosis/PDT integrated nanoplatform for melanoma therapy is constructed based on chlorin e6-modified Fe ions-doped carbon dots (Fe-CDs@Ce6). As a novel type of iron-carbon hybrid nanoparticles, the as-prepared Fe-CDs can selectively activate ferroptosis, prevent angiogenesis and inhibit the migration of mouse skin melanoma cells (B16), but have no toxicity to normal cells. The nano-conjugated structures facilitate not only the aqueous dispersibility of Ce6, but also the self-accumulation ability of Fe-CDs@Ce6 within melanoma area without requiring extra targets. Moreover, the therapeutic effects of Fe-CDs@Ce6 are synergistically enhanced due to the increased GSH depletion by PDT and the elevated singlet oxygen (1O2) production efficiency by Fe-CDs. When combined with laser irradiation, the tumor growth can be significantly suppressed by Fe-CDs@Ce6 through cyclic administration. The T2-weighted magnetic resonance imaging (MRI) capability of Fe-CDs@Ce6 also reveals their potentials for cancer diagnosis and navigation therapy. CONCLUSIONS: Our findings indicate the multifunctionality of Fe-CDs@Ce6 in effectively combining ferroptosis/PDT therapy, tumor targeting and MRI imaging, which enables Fe-CDs@Ce6 to become promising biocompatible nanoplatform for the treatment of melanoma.

High-Fluence Epithelium-off Accelerated Pulsed Corneal Cross-linking (15 mW/cm2; 7.2 J/cm2) for Pediatric Keratoconus: A 3-Year Retrospective Analysis.

PURPOSE: To assess the safety and efficacy of treatment and secondarily determine the topographic changes, visual outcomes, and demarcation line depth after high-fluence pulsed light accelerated cross-linking (ACXL) in pediatric patients (younger than 18 years) with progressive keratoconus. METHODS: This retrospective analysis included 32 eyes (25 children, aged 11 to 18 years), with progressive keratoconus treated with high-energy epithelium-off pulsed light ACXL (7.2 J/cm2, 15 mW/cm2, 12 minutes, 2 seconds on/1 second off). Corrected distance visual acuity (CDVA), Scheimpflug tomography, and anterior optical coherence tomography measurements were recorded preoperatively and 1, 2, and 3 years postoperatively. RESULTS: A total of 32 eyes were included. Significant CDVA improvement, pachymetry, and maximum keratometry reduction were found at all follow-up visits. Mean keratometric values remained stable, and astigmatism showed a mild worsening (< 0.25 D) with statistical significance at 1 and 3 years. Total aberration showed discordant results and coma aberration had a slight improvement without statistical significance. The demarcation line depth was 265 ± 26 µm. Three patients developed mild haze without visual acuity loss. None of the patients underwent a second CXL procedure. CONCLUSIONS: In pediatric patients, high-fluence epithelium-off pulsed light ACXL appears to be a safe and effective procedure to halt the progression of keratoconus, slightly improving the CDVA and keratometric values. [J Refract Surg. 2024;40(3):e148-e155.].