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Actinic keratosis (AK) is characterized by a reddish or occasionally skin-toned rough patch on sun-damaged skin, and it is regarded as a precursor to squamous cell carcinoma (SCC). Photodynamic therapy (PDT), utilizing 5-aminolevulinic acid (ALA) along with red light, is a recognized treatment option for AK that is limited by the penetration depth of light and the distribution of the photosensitizer into the skin. Cold atmospheric plasma (CAP) is a partially ionized gas with permeability-enhancing and anti-cancer properties. This study analyzed, in vitro, whether a combined treatment of CAP and ALA-PDT may improve the efficacy of the treatment. In addition, the effect of the application sequence of ALA and CAP was investigated using in vitro assays and the molecular characterization of human oral SCC cell lines (SCC-9, SCC-15, SCC-111), human cutaneous SCC cell lines (SCL-1, SCL-2, A431), and normal human epidermal keratinocytes (HEKn). The anti-tumor effect was determined by migration, invasion, and apoptosis assays and supported the improved efficacy of ALA-PDT in combination with CAP. However, the application sequence ALA-CAP–red light seems to be more efficacious than CAP-ALA–red light, which is probably due to increased intracellular ROS levels when ALA is applied first, followed by CAP and red light treatment. Furthermore, the expression of apoptosis- and senescence-related molecules (caspase-3, -6, -9, p16INK4a, p21CIP1) was increased, and different genes of the junctional network (ZO-1, CX31, CLDN1, CTNNB1) were induced after the combined treatment of CAP plus ALA-PDT. HEKn, however, were much less affected than SCC cells. Overall, the results show that CAP may improve the anti-tumor effects of conventional ALA-PDT on SCC cells. Whether this combined application is successful in treating AK in vivo has to be carefully examined in follow-up studies. [ABSTRACT FROM AUTHOR]

Currently, microbial infections have posed an arduous challenge to global public health, whereas the rise of antibiotic resistance is rendering traditional antibiotic therapies futile, prompting the development of new antimicrobial technologies. Photoactive nanomaterials have thus garnered a thriving interest for disinfection owing to their superior antibacterial efficaciousness, favorable biosafety, and rapidness and spatiotemporal precision in excreting bactericidal actions. The review summarizes recent advances and emerging trends in the design, nanoengineering, and bioapplications of photoactive antimicrobials. It commences by elaborating fundamental theories on bacterial resistance, and antibacterial mechanisms of nanomaterials and phototherapy. Subsequently, the regulation of the antibacterial effectiveness of photoactive nanomaterials is comprehensively discussed, centering on criteria and strategies for tuning photoabsorption spectra, photothermal conversion, and photocatalytic efficiency, alongside tactics for enabling synergistic therapies. This is followed by comparative analyses of techniques and modalities for synthesizing and engineering photoactive nanomaterials with diverse structures, forms, and functionalities. Thereafter, the state‐of‐the‐art applications of phototherapies across various medical sectors are portrayed, and key challenges and opportunities are finally discussed to spur future innovations and translation. This review is envisaged to provide useful guidance for devising and developing nanomaterials‐based photoresponsive antimicrobials with application‐specific materials properties and biological functions. [ABSTRACT FROM AUTHOR]

With the outbreak of the coronavirus disease 2019 (COVID-19), reductions in T-cell function and exhaustion have been observed in patients post-infection of COVID-19. T cells are key mediators of anti-infection and antitumor, and their exhaustion increases the risk of compromised immune function and elevated susceptibility to cancer. Non-small cell lung cancer (NSCLC) is the most common subtype of lung cancer with high incidence and mortality. Although the survival rate after standard treatment such as surgical treatment and chemotherapy has improved, the therapeutic effect is still limited due to drug resistance, side effects, and recurrence. Recent advances in molecular biology and immunology enable the development of highly targeted therapy and immunotherapy for cancer, which has driven cancer therapies into individualized treatments and gradually entered clinicians' views for treating NSCLC. Currently, with the development of photosensitizer materials, phototherapy has been gradually applied to the treatment of NSCLC. This review provides an overview of recent advancements and limitations in different treatment strategies for NSCLC under the background of COVID-19. We discuss the latest advances in phototherapy as a promising treatment method for NSCLC. After critically examining the successes, challenges, and prospects associated with these treatment modalities, their profound prospects were portrayed. [ABSTRACT FROM AUTHOR]

Stimulation of the innate immune stimulator of interferon genes (STING) pathway has been shown to boost anti-tumour immunity. Nevertheless, the systemic delivery of STING agonists to the tumour presents challenges. Therefore, we designed a cyclic dinucleotide (CDN)-based drug delivery system (DDS) combined photothermal therapy (PTT)/photodynamic therapy (PDT)/immunotherapy for cutaneous melanoma. We coencapsulated a reactive oxygen species (ROS)-responsive prodrug thioketone-linked CDN (TK-CDN), and photoresponsive agents chlorin E6 (Y6) within mitochondria-targeting reagent triphenylphosphonium (TPP)-modified liposomes (Lipo/TK-CDN/TPP/Y6). Lipo/TK-CDN/TPP/Y6 exhibited a photothermal effect similar to Y6, along with a superior cellular uptake rate. Upon endocytosis by B16F10 cells, Lipo/TK-CDN/TPP/Y6 generated large amounts of ROS under laser irradiation for PDT. Mice bearing B16F10 tumours were intravenously injected with Lipo/TK-CDN/TPP/Y6 and exposed to irradiation, resulting in a substantial inhibition of tumour growth. Exploration of the mechanism of anti-tumour action showed that Lipo/TK-CDN/TPP/Y6 had a stronger stimulation of STING activation and anti-tumour immune cell infiltration compared to other groups. Hence, the Lipo/TK-CDN/TPP/Y6 nanoparticles offer great potential as a DDS for targeted and on-demand drug release at tumour sites. These nanoparticles exhibit promise as a candidate for precise and controllable combination therapy in the treatment of tumours. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 is a highly pathogenic virus responsible for the COVID-19 disease. It belongs to the Coronaviridae family, characterized by a phospholipid envelope, which is crucial for viral entry and replication in host cells. Hypericin, a lipophilic, naturally occurring photosensitizer, was reported to effectively inactivate enveloped viruses, including SARS-CoV-2, upon light irradiation. In addition to its photodynamic activity, Hyp was found to exert an antiviral action also in the dark. This study explores the mechanical properties of heat-inactivated SARS-CoV-2 viral particles using Atomic Force Microscopy (AFM). Results reveal a flexible structure under external stress, potentially contributing to the virus pathogenicity. Although the fixation protocol causes damage to some particles, correlation with fluorescence demonstrates colocalization of partially degraded virions with their genome. The impact of hypericin on the mechanical properties of the virus was assessed and found particularly relevant in dark conditions. These preliminary results suggest that hypericin can affect the mechanical properties of the viral envelope, an effect that warrants further investigation in the context of antiviral therapies. [ABSTRACT FROM AUTHOR]

Gliomas account for 24% of all the primary brain and Central Nervous System (CNS) tumors. These tumors are diverse in cellular origin, genetic profile, and morphology but collectively have one of the most dismal prognoses of all cancers. Work is constantly underway to discover a new effective form of glioma therapy. Photodynamic therapy (PDT) may be one of them. It involves the local or systemic application of a photosensitive compound—a photosensitizer (PS)—which accumulates in the affected tissues. Photosensitizer molecules absorb light of the appropriate wavelength, initiating the activation processes leading to the formation of reactive oxygen species and the selective destruction of inappropriate cells. Research focusing on the effective use of PDT in glioma therapy is already underway with promising results. In our work, we provide detailed insights into the molecular changes in glioma after photodynamic therapy. We describe a number of molecules that may contribute to the resistance of glioma cells to PDT, such as the adenosine triphosphate (ATP)-binding cassette efflux transporter G2, glutathione, ferrochelatase, heme oxygenase, and hypoxia-inducible factor 1. We identify molecular targets that can be used to improve the photosensitizer delivery to glioma cells, such as the epithelial growth factor receptor, neuropilin-1, low-density lipoprotein receptor, and neuropeptide Y receptors. We note that PDT can increase the expression of some molecules that reduce the effectiveness of therapy, such as Vascular endothelial growth factor (VEGF), glutamate, and nitric oxide. However, the scientific literature lacks clear data on the effects of PDT on many of the molecules described, and the available reports are often contradictory. In our work, we highlight the gaps in this knowledge and point to directions for further research that may enhance the efficacy of PDT in the treatment of glioma. [ABSTRACT FROM AUTHOR]

Wound-associated infections represent an arduous global healthcare challenge, especially in the "post-antibiotic" era, necessitating the development of advanced antimicrobial dressing materials that simultaneously dictate the use of rapid yet effective disinfection, low drug resistance and side effects, and the potency to foster tissue healing. Nanoantimicrobial-armored nanostructured functional dressing systems have piqued extensive interest to satisfy these criteria. Herein, fusing electrospinning nanotechnology and an emerging photo–chemo synergistic sterilization paradigm, a smart "all-in-one" multifunctional wound-managing dressing platform was constructed, through incorporating photochemically active nanocrystalline cuprous oxide (Cu2O) into modified polycaprolactone (mPCL) electrospun fibrous mats. The resulting materials were systematically characterized pertaining to physiochemical analysis, photoabsorption and photocurrent measurements, and photocatalytic reactive oxygen species (ROS) generation. The capability of this nanoplatform to elicit rapid, photoactivated, catalytically augmented bacterial disinfection was corroborated, displaying ∼99–100% broad-spectrum antibacterial efficacies against Staphylococcus aureus and Escherichia coli in 25 min. Benefiting from the release of Cu2+, mPCL-Cu2O impairs bacterial contamination even under dark conditions. Furthermore, these materials also exhibited favorable in vitro/-ovo biocompatibility toward NIH3T3 fibroblasts, red blood cells, and chick chorioallantoic membrane, alongside appreciable pro-healing capacity in bridging scratch-based wounds, which could be attributed to nanofiber-afforded biomimetic topography and controllable liberation of micronutrient Cu ions. This study provides insights into the design and fabrication of simple yet smart antibacterial nanoplatforms for biomedical applications. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) has shown promise as a modality for the treatment of cervical cancer caused by the human papillomavirus (HPV). This review provides a comprehensive examination of the role of PDT in overcoming the challenges presented by conventional treatments for cervical cancer. Beginning with an overview of the relationship between cervical cancer and HPV infection, the review introduces the principles of PDT, its mechanism of action, and its potential as an innovative treatment strategy. The review highlights preclinical studies in animal models that demonstrate the efficacy of PDT in targeting HPV-infected cervical cells and provide mechanistic insights into its cytotoxic effects. We reviewed clinical studies and case reports highlighting the potential of PDT as an alternative or adjunctive treatment option. Challenges and limitations, including depth of light penetration, photosensitizer specificity, and standardization of protocols, will be discussed in the context of potential side effects and comparison with conventional treatments. Future directions include ongoing research, combination therapies with immunotherapy or targeted agents, advances in photosensitizer development, and personalized approaches. The advancement of PDT promises to change the landscape of HPV-associated cervical cancer treatment by providing a targeted, personalized, and minimally invasive approach.

Biofilm-associated infections pose a significant challenge in healthcare, constituting 80% of bacterial infections and often leading to persistent, chronic conditions. Conventional antibiotics struggle with efficacy against these infections due to the high tolerance and resistance induced by bacterial biofilm barriers. Two-dimensional nanomaterials, such as those from the graphene family, boron nitride, molybdenum disulfide (MoS2), MXene, and black phosphorus, hold immense potential for combating biofilms. These nanomaterial-based antimicrobial strategies are novel tools that show promise in overcoming resistant bacteria and stubborn biofilms, with the ability to circumvent existing drug resistance mechanisms. This review comprehensively summarizes recent developments in two-dimensional nanomaterials, as both therapeutics and nanocarriers for precision antibiotic delivery, with a specific focus on nanoplatforms coupled with photothermal/photodynamic therapy in the elimination of bacteria and penetrating and/or ablating biofilm. This review offers important insight into recent advances and current limitations of current antibacterial nanotherapeutic approaches, together with a discussion on future developments in the field, for the overall benefit of public health. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is significantly contributed to global cancer mortality rates. Treating CRC is particularly challenging due to metastasis and drug resistance. There is a pressing need for new treatment strategies against metastatic CRC. Photodynamic therapy (PDT) offers a well-established, minimally invasive treatment option for cancer with limited side effects. Hypericin (HYP), a potent photosensitizer for PDT, has been documented to induce cytotoxicity and apoptosis in various types of cancers. However, there are few reports on the inhibitory effects of HYP-mediated PDT on the metastatic ability of CRC cells. Here, we evaluate the inhibitory effects of HYP-mediated PDT against metastatic CRC cells and define its underlying mechanisms. Wound-healing and Transwell assays show that HYP-mediated PDT suppresses migration and invasion of CRC cells. F-actin visualization assays indicate HYP-mediated PDT decreases F-actin formation in CRC cells. TEM assays reveal HYP-mediated PDT disrupts pseudopodia formation of CRC cells. Mechanistically, immunofluorescence and western blotting results show that HYP-mediated PDT upregulates E-cadherin and downregulates N-cadherin and Vimentin. HYP-mediated PDT also suppresses key EMT regulators, including Snail, MMP9, ZEB1 and α-SMA. Additionally, the expressions of RhoA and ROCK1 are downregulated by HYP-mediated PDT. Together, these findings suggest that HYP-mediated PDT inhibits the migration and invasion of HCT116 and SW620 cells by modulating EMT and RhoA–ROCK1 signaling pathway. Thus, HYP-mediated PDT presents a potential therapeutic option for CRC. [ABSTRACT FROM AUTHOR]

The application of transition metal complexes for antimicrobial photodynamic therapy (PDT) has emerged as an attractive alternative in mitigating a broad range of bacterial pathogens, including multidrug‐resistant pathogens. In view of their photostability, long excited‐state lifetimes, and tunable emission properties, transition metal complexes also contribute as bioimaging agents. In the present work, we designed mono and trinuclear cyclometalated iridium (III) complexes to explore their imaging application and antibacterial potential. For this, we used Methicillin‐resistant S. aureus (MRSA), the most prevalent of community‐associated (CA) multidrug‐resistant (MDR) bacteria (CA MDR) and Lactococcus lactis (L. lactis) as Gram‐positive while Campylobacter jejuni (C. jejuni) and E. coli as Gram‐negative bacteria. In addition to differential bioimaging of these bacteria, we assessed the antibacterial effects of both mono and trinuclear Ir(III) complexes under exposure to 427 nm LED light. The data presented herein strongly suggest better efficacy of trinuclear Ir(III) complex over the mononuclear complex in imparting photoinduced cell death of MRSA. Based on the safety profile of these complexes, we propose that trinuclear cyclometalated iridium(III) complex holds great promise for selective recognition and targeting MDR bacteria with minimal off‐target effect. [ABSTRACT FROM AUTHOR]

Purpose: Molecular oxygen, besides a photosensitizer and light of appropriate wavelength, is one of the three factors necessary for photodynamic therapy (PDT). In tumor tissue, PDT leads to the killing of tumor cells, destruction of endothelial cells and vasculature collapse, and the induction of strong immune responses. All these effects may influence the oxygenation levels, but it is the vasculature changes that have the main impact on pO2. The purpose of our study was to monitor changes in tumor oxygenation after PDT and explore its significance for predicting long-term treatment response. Procedures: Electron paramagnetic resonance (EPR) spectroscopy enables direct, quantitative, and sequential measurements of partial pressure of oxygen (pO2) in the same animal. The levels of chlorophyll derived photosensitizers in tumor tissue were determined by transdermal emission measurements. Results: The noninvasive monitoring of pO2 in the tumor tissue after PDT showed that the higher ΔpO2 (pO2 after PDT minus pO2 before PDT), the greater the inhibition of tumor growth. ΔpO2 also correlated with higher levels of the photosensitizers in the tumor and with the occurrence of a severe edema/erythema after PDT. Conclusion: Monitoring of PDT-induced changes in tumor oxygenation is a valuable prognostic factor and could be also used to identify potentially resistant tumors, which is important in predicting long-term treatment response. [ABSTRACT FROM AUTHOR]

Cancer therapy, especially for tumors near sensitive areas, demands precise treatment. This review explores photodynamic therapy (PDT), a method leveraging photosensitizers (PS), specific wavelength light, and oxygen to target cancer effectively. Recent advancements affirm PDT's efficacy, utilizing ROS generation to induce cancer cell death. With a history spanning over decades, PDT's dynamic evolution has expanded its application across dermatology, oncology, and dentistry. This review aims to dissect PDT's principles, from its inception to contemporary medical applications, highlighting its role in modern cancer treatment strategies. [ABSTRACT FROM AUTHOR]

Pathological scars (PS), including hypertrophic scars (HTS) and keloids, are a common complication of poor wound healing that significantly affects patients' quality of life. Currently, there are several treatment options for PS, including surgery, drug therapy, radiation therapy, and biological therapy. However, these treatments still face major challenges such as low efficacy, high side effects, and a high risk of recurrence. Therefore, the search for safer and more effective treatments is particularly urgent. New materials often have less immune rejection, good histocompatibility, and can reduce secondary damage during treatment. New technology can also reduce the side effects of traditional treatments and the recurrence rate after treatment. Furthermore, derivative products of new materials and biomaterials can improve the therapeutic effect of new technologies on PS. Therefore, new technologies and innovative materials are considered better options for enhancing PS. This review concentrates on the use of two emerging technologies, microneedle (MN) and photodynamic therapy (PDT), and two novel materials, photosensitizers and exosomes (Exos), in the treatment of PS. [ABSTRACT FROM AUTHOR]

Preparation of Cu@MIL-101@PMTPC nanomedicine and schematic mechanism for effective and safe tumor therapy using this nano-loaded platform in combination with chemical kinetics/photodynamics/immuno-effects and chemotherapy. [Display omitted] Tumors produce a hypoxic environment that greatly influences cancer treatment, and conventional chemotherapeutic drugs cannot selectively accumulate in the tumor region because of the lack of a tumor targeting mechanism, causing increased systemic toxicities and side effects. Hence, designing and developing new nanoplatforms that combine multimodal therapeutic regimens is essential to improve tumor therapeutic efficacy. Herein, we report the synthesis of ultrafine Cu nanoparticles loaded with a drug combination of cisplatin (Pt) and 1-methyl- d -tryptophan (1-MT) and externally coated with 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin (TCPP) photosensitizer, polydopamine (PDA) and CaO 2 of MIL-101(Fe) as a new nanoplatform (Cu@MIL-101@PMTPC). The nanoplatform synergistically combined chemodynamic therapy (CDT), photodynamic therapy (PDT), and immunochemotherapy. The Fe3+ in MIL-101(Fe) and the surface Cu nanoparticles exhibited strong ability to consume intracellular glutathione (GSH), thereby generating a Fenton-like response in the tumor microenvironment (TME) with substantial peroxidase (POD)-like and superoxide dismutase (SOD)-like activities. In this design, we used the indoleamine 2,3-dioxygenase (IDO) inhibitor 1-MT to overcome chemotherapy-induced immune escape phenomena including enhanced CD8+ and CD4+ T cell expression, interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) production, and accelerated immunogenic cell death. The targeted release of cisplatin loaded into Cu@MIL-101@PMTPC also reduced toxic side effects of chemotherapy. TCPP generated a large amount of singlet oxygen (1O 2) upon specific laser irradiation to effectively kill tumor cells. CaO 2 on the outer layer generated oxygen (O 2) and hydrogen peroxide (H 2 O 2) to ameliorate hypoxia in the tumor microenvironment, enhance the PDT effect, and provide a continuous supply of H 2 O 2 for the Fenton-like reaction. Thus, this nanocarrier platform exhibited a powerful chemodynamic, photodynamic, and immunochemotherapeutic cascade, providing a new strategy for cancer treatment. [ABSTRACT FROM AUTHOR]

Background: Photodynamic therapy (PDT) can be a promising alternative for patients with acne vulgaris. Our study aimed to evaluate the efficacy and safety of red light photodynamic therapy with BF-200 ALA gel in the treatment of different types of acne vulgaris. Methods: We performed a retrospective, observational study of a series of 22 cases. All patients were treated according to a mild PDT protocol. After a careful wash of the affected skin areas, BF-200 ALA gel was applied to the skin in a thin layer and incubated for 30 min, followed by illumination using narrow-spectrum red light (635 nm) at a dose of 4 J/cm2. Most patients received one (36.4%), two (27.3%), or three (22.7%) PDT sessions. About a third of the patients received concomitant acne treatment with topical retinoids. Results: Patients of 25.1 ± 8.9 years suffering from papulopustular (45.5%), nodular (27.3%), and comedonal acne (27.3%) in the face were included. Irrespective of acne type or severity, 95.5% of patients had good or excellent responses to the treatment with PDT (≥60% lesion clearance). We found no association between concomitant acne medication and the favorable results achieved by PDT. Most patients reported no adverse events (72.7%), except for six patients who experienced erythema. The good efficacy results were maintained over a follow-up period of 12.5 ± 10.8 months. Conclusions: In this study, we show that PDT with BF-200 ALA gel and low light dose is an effective and long-lasting option for the treatment of different acne types. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) shows promise in tumor treatment, particularly when combined with nanotechnology. This study examines the impact of deep learning, particularly the Cellpose algorithm, on the comprehension of cancer cell responses to PDT. The Cellpose algorithm enables robust morphological analysis of cancer cells, while logistic growth modelling predicts cellular behavior post-PDT. Rigorous model validation ensures the accuracy of the findings. Cellpose demonstrates significant morphological changes after PDT, affecting cellular proliferation and survival. The reliability of the findings is confirmed by model validation. This deep learning tool enhances our understanding of cancer cell dynamics after PDT. Advanced analytical techniques, such as morphological analysis and growth modeling, provide insights into the effects of PDT on hepatocellular carcinoma (HCC) cells, which could potentially improve cancer treatment efficacy. In summary, the research examines the role of deep learning in optimizing PDT parameters to personalize oncology treatment and improve efficacy. [ABSTRACT FROM AUTHOR]

Background: Photodynamic therapy (PDT) is a cancer-targeted treatment that uses a photosensitizer (PS) and irradiation of a specific wavelength to exert cytotoxic effects. To enhance the antitumor effect against head and neck squamous cell carcinoma (HNSCC), we developed a new phototherapy, intelligent targeted antibody phototherapy (iTAP). This treatment uses a combination of immunotoxin (IT) and a PS for PDT and light irradiation. In our prior study, we demonstrated that an immunotoxin (IT) consisting of an anti-ROBO1 antibody conjugated to saporin, when used in combination with the photosensitizer (PS) disulfonated aluminum phthalocyanine (AlPcS2a) and irradiated with light at the appropriate wavelength, resulted in increased cytotoxicity against head and neck squamous cell carcinoma (HNSCC) cells. ROBO1 is a receptor known to be involved in the progression of cancer. In this study, we newly investigate the iTAP targeting epidermal growth factor receptor (EGFR) which is widely used as a therapeutic target for HNSCC. Methods: We checked the expression of EGFR in HNSCC cell lines, SAS, HO-1-u-1, Sa3, and HSQ-89. We analyzed the cytotoxicity of saporin-conjugated anti-EGFR antibody (cetuximab) (IT-Cmab), mono-L-aspartyl chlorin e6 (NPe6, talaporfin sodium), and light (664 nm) irradiation (i.e., iTAP) in SAS, HO-1-u-1, Sa3, and HSQ-89 cells. Results: EGFR was expressed highly in Sa3, moderately in HO-1-u-1, SAS, and nearly not in HSQ-89. Cmab alone or IT-Cmab alone did not show cytotoxic effects in Sa3, HO-1-u-1, and HSQ-89 cells, which have moderate or low expression levels of EGFR protein. However, the iTAP method enhanced the cytotoxicity of IT-Cmab by the photodynamic effect in Sa3 and HO-1-u-1 cells, which have moderate levels of EGFR expression. Conclusion: Our study is the first to report on the iTAP method using IT-Cmab and NPe6 for HNSCC. The cytotoxic effects are enhanced in cell lines with moderate levels of EGFR protein expression, but not in nonexpressing cell lines, which is expected to expand the range of therapeutic windows and potentially reduce complications. [ABSTRACT FROM AUTHOR]

Background: Postoperative recurrence of tongue squamous cell carcinoma (TSCC) has always been a clinical problem for patients and doctors. Surgery and radiotherapy are the main treatment methods for TSCC, but reoperation often leads to functional impairment. Side effects of radiotherapy include mucosal gland damage, dry mouth, weakened or lost taste. Improved treatment is needed. Objective: To evaluate the clinical outcome of a patient with TSCC treated with Microdrop aminolevulinic acid (ALA) photodynamic treatment (PDT) twice. Methods: ALA was dissolved in 5 % lidocaine and the concentration of ALA was 20 % by Microdrop method. Then, the tumor tissue was expanded 1 cm outward, and the injection points were evenly distributed with an upper and lower left and right interval of 2–3 mm. The 1 ml syringe was used to perform the injection in the skin of the tumor area, and there was a small cuticle at each injection point. A pathologically confirmed patient with TSCC received twice Microdrop ALA-PDT treatments, which were evaluated at 1 month and 4 months later. Results: After 3 h of Microdrop ALA injection, the wavelength of semiconductor laser was set to 630 nm, and the energy of 300 mW /cm2 was irradiated for 30 min. After two treatments, the lesions were not visible, and no recurrence occurred after 4 months of follow-up. The patient's tongue function was well preserved and the cosmetic effect was good. Conclusion: Microdrop ALA-PDT may be effective in the salvage treatment of select tongue squamous cell carcinoma.

Local hypoxia in tumors poses significant challenges to the effectiveness of oxygen-dependent photodynamic therapy (PDT). Herein, a versatile mitochondrial targeting and pH-responsive nanozyme platform (noted as Mito CPs-p) is developed for solving local hypoxia in tumors and enhancing the PDT efficiency. Mito CPs-p, which consists of carbon-dot-supported atomically dispersed platinum (CPs) with further surface modifications of triphenylphosphine (PPh3) and pH-responsive porphyrin polymers. The PDT of Mito CPs-p was activated in acidic tumor microenvironment and exposed platinum for catalyzing endogenous H2O2 decomposition to produce O2 at tumor sites, due to the hydrophobic-hydrophilic transition of pH-responsive porphyrin-containing polymers in Mito CPs-p from hydrophobic to hydrophilic, which can markedly enhance PDT efficiency. Besides, the rational integration of mitochondria-targeting will improve the bioavailability of reactive oxygen species and further strengthen the PDT efficiency. In vitro results indicated that Mito CPs-p has exhibited excellent mitochondrial targeting capability and the ROS yield of Mito CPs-p was dramatically amplified. In vivo data further revealed that the Mito CPs-p displayed superb therapeutic efficacy. Hence, the Mito CPs-p provides new insights for efficient PDT in hypoxia solid tumors.

Background: Diabetic foot ulcer (DFU) is a chronic and challenging condition, addressed through various treatments including photodynamic therapy (PDT) and standard of care (SOC), yet lacking consensus on the optimal approach. This study presents a comprehensive meta-analysis of randomized controlled trials to evaluate the efficacy and safety of PDT versus SOC in managing DFU. Methods: An extensive literature search was conducted across PubMed, Embase, and the Cochrane Library databases to identify RCTs that compared the effectiveness of PDT with SOC in treating DFU. The primary metrics evaluated included changes in ulcer area, wound healing indices, and pain levels experienced by the patients. Results: This meta-analysis incorporated data from 6 RCTs, encompassing 458 patients with 467 DFUs. The analysis indicated that while PDT led to a faster reduction in ulcer size compared to SOC, the difference was not statistically significant [mean difference (MD): 2.73cm², 95 % Confidence Interval (CI) -2.98 to 8.44; p > 0.05]. However, a notable improvement was observed in the wound healing rate in the PDT group [MD: 29.26 %, 95 % CI 7.24 to 51.28; p = 0.01]. Based on the Visual Analog Scale (VAS), pain assessment revealed no significant difference between the two treatment groups [MD: 2.35, 95 % CI -2.36 to 7.06; p = 0.33]. Conclusion: The study suggests that PDT might offer an enhanced healing rate for DFUs compared to SOC alone, potentially leading to improved patient outcomes. Importantly, our findings highlight the superiority of photodynamic therapy in accelerating ulcer healing without an associated increase in complications. PROSPERO: 2023 CRD42023493930

Background: Prevention of high-risk HPV (HR-HPV) infection and effective medical intervention of persistent HPV infection and precancerous lesions are critical for the prevention of cervical cancer. Aims: The aim of this retrospective comparative study was to evaluate the outcomes of ALA PDT and observation only in the management of low-grade squamous intraepithelial lesions (LSIL). Methods: In PDT Group (n = 138), ALA PDT was applied to patients with colposcopic biopsy confirmed cervical LSIL accompanied with HR-HPV infection longer than 1 year or HPV 16/18 subtype infection. Cervical LSIL only patients received 3 times of ALA PDT and those with concurrent cervical canal or vaginal lesions received 6 times ALA PDT. Control Group (n = 69) received observation only. Colposcopy, TCT and HPV typing were performed before and after treatment. Patients were followed up for up to two years. Result: The observation group showed 26.1%, 34.8% and 53.6% HR-HPV negative conversion at 3-6, 12 and 24 months, respectively. LSIL regression rate of the observation group was 33.33%, 36.23% and 65.22% at 3-6, 12 and 24 months, respectively. There was 62.32%, 80.56% and 89.22% patients achieved HPV clearance at 3-6, 12 and 24 months after PDT treatment, respectively. The LSIL remission rate was 89.86%, 94.40% and 96.08% at 3-6, 12 and 24 months after ALA PDT, respectively. The abnormal TCT (≧ ASCUS) was reduced from 92% to 10.1%, 4.6% and 3.9% at 3-6, 12 and 24 months after ALA PDT, respectively. The patient age was not a factor affecting the clearance of HPV infection and the LSIL regression rate of PDT treatment. Conclusions: This study demonstrates that the application of multiple ALA PDT treatments has added value in achieving both short-term and long-term HPV and lesion clearance.

Abstract Background Photodynamic therapy (PDT) is a promising interventional treatment approach that contributes to antitumor immunity. It has been reported that PDT can enhance the effectiveness of immune checkpoint inhibitors (ICIs), but its mechanism is yet unclear. Herein, we implemented bioinformatics analysis to detect common pathways and potential biomarkers in non-small cell lung cancer (NSCLC), PDT, and NSCLC immunotherapy to investigate potential links between PDT, immunotherapy and NSCLC, and their clinical impact. Methods Differentially expressed genes in NSCLC- and NSCLC immunotherapy-related data in the GEO database were intersected with PDT-related genes in the GeneCards database to obtain candidate genes and shared pathways. Enrichment analysis and protein–protein interaction were established to identify key genes in functionally enriched pathways. The expression profiles and the prognostic significance of key genes were depicted. Results Bioinformatics analysis showed that HIF-1α was screened as a prognostic gene in hypoxia, HIF-1, and PD-L1-related signaling pathways, which was associated with clinical response in NSCLC patients after PDT and immunotherapy. In vivo experiments showed that PDT could inhibit tumor growth and upregulate HIF-1α and PD-L1 expressions in NSCLC tissues with a positive correlation, which might influence the blocking activity of ICIs on the HIF-1, and PD-L1-related signaling pathways. Conclusions PDT might improve the clinical response of ICIs by upregulating tumor HIF-1α and PD-L1 expressions in NSCLC.

Upconversion photodynamic therapy (UC-PDT), which integrates upconversion nanoparticles (UCNPs) with photosensitizers (PSs), presents a promising advancement in the field of phototherapy. However, despite the extensive studies focused on the design and synthesis of UCNPs, there is a paucity of systematic research on the mechanisms underlying the synergistic upconversion photodynamic effects. Here we have synthesized upconversion core@dotted-shell nanoparticles (CDSNPs) and covalently tethered them with two distinct PSs, thereby constructing a dual-PS UC-PDT system with high synergistic photodynamic performance. To unravel the mechanism underlying the synergism, we employed a combination of quantum mechanical calculations and ultrafast time-resolved spectroscopy techniques. The results indicate that rare earth oxides play a pivotal role in enhancing the intersystem crossing processes of PSs through modulating their excited electronic states. Additionally, Förster resonance energy transfer between two distinct PSs contributes to the amplification of triplet state populations, thus further enhancing the photodynamic effect. In vitro experiments demonstrate that the prepared CDSNPs based dual-PS system exhibits excellent biocompatibility with normal cells and exceptional synergistic photodynamic efficacy against tumor cells upon near-infrared excitation. This research contributes theoretical insights into the design and application of multi-photosensitizer UC-PDT systems, laying the groundwork for more efficient preclinical implementations in the future.

How to develop antitumor nanodrugs with low toxicity and a good curative effect is an urgent problem in the current biomedicine field. In this work, different proposed composites were simulated by the finite difference time domain (FDTD) and COMSOL, including the material element, refractive index, particle size, and shape. Also, different machine learning algorithms are utilized to predict the absorbance at the near-infrared laser of 980 nm of different materials. Through train, validation, and test, the prediction of the as-synthesized Pt–Mn has high absorbance. Then, inorganic Pt–Mn was coated with PEI in order to improve their biocompatibility. Pt–Mn nanoparticles can generate ROS under the single 980 nm laser irradiation as a photodynamic therapy (PDT) agent and as a photothermal therapy (PTT) agent to heat the cells with a photothermal conversion efficiency of 23.6%. In addition, the electrochemical and in vitro chemodynamic therapy (CDT) experiments prove that Pt–Mn nanozymes could mimic the activity of peroxidase and enhance the Fenton reaction, thereby catalyzing excess H2O2 to produce hydroxyl free radicals and illustrating the potential to induce tumor cell apoptosis as the CDT agent in a weakly acidic tumor environment to complete high-efficiency chemokinetic therapy. Finally, Pt–Mn–PEI nanoparticles were used for PDT/PTT/CDT and the immune checkpoint inhibitor of anti-PD-L1 is injected in order to obtain the assistant immunotherapy, providing a potential choice to anticancer through effective synergistic cancer therapies. [ABSTRACT FROM AUTHOR]

Nosocomial infections are a significant threat to public health that leads to substantial morbidity and mortality. The emergence and spread of antibiotic-resistant organisms have compounded the complexity of managing these infections, highlighting the urgent need for innovative and effective strategies to combat them. Photostimuli-responsive nanomaterials have emerged as promising tools for coating biomedical devices and tools against nosocomial infections due to their ability to selectively target and kill pathogenic bacteria and fungi. It is feasible to develop antibacterial surfaces by integrating photothermal agents (PTAs), photodynamic agents (PDAs), and both PTAs and PDAs into coatings. When exposed to light, PTAs generate heat that can be used to kill bacteria, while PDAs emit reactive oxygen species (ROS) that can also be used to kill bacteria. The combination of photothermal and photodynamic therapies produces a synergistic effect in which the death of bacteria is boosted in comparison with the use of each individual therapy. These coatings have the potential to provide enhanced bacterial control for a number of biomedical devices, including implants, catheters, meshes, and wound dressings. The utilization of antimicrobial nanomaterials offers a promising approach for reducing the risk of infections associated with the use of these devices. [ABSTRACT FROM AUTHOR]

Background: Photodynamic therapy (PDT) is a promising interventional treatment approach that contributes to antitumor immunity. It has been reported that PDT can enhance the effectiveness of immune checkpoint inhibitors (ICIs), but its mechanism is yet unclear. Herein, we implemented bioinformatics analysis to detect common pathways and potential biomarkers in non-small cell lung cancer (NSCLC), PDT, and NSCLC immunotherapy to investigate potential links between PDT, immunotherapy and NSCLC, and their clinical impact. Methods: Differentially expressed genes in NSCLC- and NSCLC immunotherapy-related data in the GEO database were intersected with PDT-related genes in the GeneCards database to obtain candidate genes and shared pathways. Enrichment analysis and protein–protein interaction were established to identify key genes in functionally enriched pathways. The expression profiles and the prognostic significance of key genes were depicted. Results: Bioinformatics analysis showed that HIF-1α was screened as a prognostic gene in hypoxia, HIF-1, and PD-L1-related signaling pathways, which was associated with clinical response in NSCLC patients after PDT and immunotherapy. In vivo experiments showed that PDT could inhibit tumor growth and upregulate HIF-1α and PD-L1 expressions in NSCLC tissues with a positive correlation, which might influence the blocking activity of ICIs on the HIF-1, and PD-L1-related signaling pathways. Conclusions: PDT might improve the clinical response of ICIs by upregulating tumor HIF-1α and PD-L1 expressions in NSCLC. [ABSTRACT FROM AUTHOR]

The persistent failure of standard chemotherapy underscores the urgent need for innovative and targeted approaches in cancer treatment. Photodynamic therapy (PDT) has emerged as a promising photochemistry-based approach to address chemoresistance in cancer regimens. PDT not only induces cell death but also primes surviving cells, enhancing their susceptibility to subsequent therapies. This review explores the principles of PDT and discusses the concept of photodynamic priming (PDP), which augments the effectiveness of treatments like chemotherapy. Furthermore, the integration of nanotechnology for precise drug delivery at the right time and location and PDT optimization are examined. Ultimately, this study highlights the potential and limitations of PDT and PDP in cancer treatment paradigms, offering insights into future clinical applications. [ABSTRACT FROM AUTHOR]

Single-molecule-based synergistic phototherapy holds great potential for antimicrobial treatment. Herein, we report an orthogonal molecular cationization strategy to improve the reactive oxygen species (ROS) and hyperthermia generation of heptamethine cyanine (Cy7) for photodynamic and photothermal treatments of bacterial infections. Cationic pyridine (Py) is introduced at the meso‑position of the asymmetric Cy7 with intramolecular charge transfer (ICT) to construct an atypical electron-transfer triad, which reduces ΔE S1-S0 , circumvents rapid charge recombination, and simultaneously enhances intersystem crossing (ISC) based on spin-orbit charge-transfer ISC (SOCT-ISC) mechanism. This unique molecular construction produces anti-Stokes luminescence (ASL) because the rotatable C N bond enriched in high vibrational-rotational energy levels improves hot-band absorption (HBA) efficiency. The obtained triad exhibits higher singlet oxygen quantum yield and photothermal conversion efficiency compared to indocyanine green (ICG) under irradiation above 800 nm. Cationization with Py enables the triad to target bacteria via intense electrostatic attractions, as well as biocidal property against a broad spectrum of bacteria in the dark. Moreover, the triad under irradiation can enhance biofilm eradication performance in vitro and statistically improve healing efficacy of MRSA-infected wound in mice. Thus, this work provides a simple but effective strategy to design small-molecule photosensitizers for synergistic phototherapy of bacterial infections. We developed an orthogonal molecular cationization strategy to enhance the reactive oxygen species and thermal effects of heptamethine cyanine (Cy7) for photodynamic and photothermal treatments of bacterial infections. Specifically, cationic pyridine (Py) was introduced at the meso ‑position of the asymmetric Cy7 to construct an atypical electron-transfer triad, which reduced ΔE S1-S0 , circumvented rapid charge recombination, and simultaneously enhanced intersystem crossing (ISC). This triad, with a rotatable C N bond, produced anti-Stokes luminescence due to hot-band absorption. The triad enhanced antimicrobial performance and statistically improved the healing efficacy of MRSA-infected wounds in mice. This site-specific cationization strategy may provide insights into the design of small molecule-based photosensitizers for synergistic phototherapy of bacterial infections. [Display omitted] [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a minimally invasive treatment that uses the combination of a photosensitizing agent (PS) and light to selectively target solid tumors, as well as several non-neoplastic proliferating cell diseases. After systemic administration, PSs are activated by localized irradiation with visible light; in the presence of adequate concentrations of molecular oxygen, this causes the formation of reactive oxygen species (ROS) and subsequent tissue damage. In this study, two series of tetrakis(N-alkylpyridinium-4-yl)porphyrins were synthesized, differing in the presence or absence of a zinc ion in the tetrapyrrole nucleus, as well as in the N-alkyl chain length (from one to twelve carbon atoms). The compounds were chemically characterized, and their effect on cell viability was evaluated using a panel of three tumor cell lines to determine a possible relationship between photodynamic activity and Zn presence/alkyl chain length. The types of cell death mechanisms involved in the effect of the various PSs were also evaluated. The obtained results indicate that the most effective porphyrin is the Zn-porphyrin, with a pendant made up of eight carbon atoms (Zn-C8). [ABSTRACT FROM AUTHOR]

This review is concerned with chronic wounds, with an emphasis on biofilm and its complicated management process. The basics of antimicrobial photodynamic therapy (PDT) and its underlying mechanisms for microbial eradication are presented. Intrinsically active nanocarriers (polydopamine NPs, chitosan NPs, and polymeric micelles) that can further potentiate the antimicrobial photodynamic effect are discussed. This review also delves into the role of photoactive electrospun nanofibers, either in their eluting or non-eluting mode of action, in microbial eradication and accelerating the healing of wounds. Synergic strategies to augment the PDT-mediated effect of photoactive nanofibers are reviewed. [ABSTRACT FROM AUTHOR]

Simple Summary: Photodynamic therapy (PDT) has emerged as a versatile treatment option for head and neck disorders. The purpose of our review was to provide an overview of the use of PDT therapy in a variety of diseases. The use of PDT therapy has recently emerged as an innovative and effective method of cancer treatment. However, more and more studies are showing that it is also promising for treating a variety of non-cancerous lesions, providing a minimally invasive alternative for certain conditions. The same following principles apply: the application of a photosensitizer, exposure to light, and then the destruction of abnormal cells. In our work, we highlighted the importance of photodynamic therapy and its valuable treatment as an option for a variety of diseases of the head and neck area, not just cancer. With this, we want to encourage researchers to more widely use photodynamic therapy in head and neck disorders. Photodynamic therapy (PDT) has emerged as a promising modality for the treatment of various diseases. This non-invasive approach utilizes photosensitizing agents and light to selectively target and destroy abnormal cells, providing a valuable alternative to traditional treatments. Research studies have explored the application of PDT in different areas of the head. Research is focusing on a growing number of new developments and treatments for cancer. One of these methods is PDT. Photodynamic therapy is now a revolutionary, progressive method of cancer therapy. A very important feature of PDT is that cells cannot become immune to singlet oxygen. With this therapy, patients can avoid lengthy and costly surgeries. PDT therapy is referred to as a safe and highly selective therapy. These studies collectively highlight the potential of PDT as a valuable therapeutic option in treating the head area. As research in this field progresses, PDT may become increasingly integrated into the clinical management of these conditions, offering a balance between effectiveness and minimal invasiveness. [ABSTRACT FROM AUTHOR]

Oral cancer is a disease with high morbidity and mortality worldwide and greatly impacts the quality of life, especially in patients with advanced stages. Photodynamic therapy (PDT) is one of the most effective clinical treatments for oral cancers. However, most clinically applied photosensitizers have several deficiencies, including oxygen dependence, poor aqueous solubility, and a lack of tumor-targeting ability. Herein, the carrier-free multifunctional Sorafenib (Sor), chlorin e6 (Ce6), and Fe3+ self-assembly co-delivery nanoparticles (Sor-Ce6 NPs) were constructed via combining a ferroptosis inducer Sor and a photosensitizer Ce6 for synergetic therapy. The as-synthesized Sor-Ce6 NPs presented excellent colloidal stability and water dispersity with good in vivo tumor-targeting ability. More significantly, the low dose of Sor-Ce6 NPs had little dark toxicity but produced significantly enhanced ROS and supplied O 2 sustainably to increase phototoxicity through ferroptosis pathway. Notably, the Sor-Ce6 NPs showed significantly higher in vitro and in vivo anti-tumor efficacy than the Sor/Ce6 mixture due to the improvement of cellular uptake and the incorporation of foreign Fe ions in the system, which also confer the T 1 magnetic resonance-guided imaging ability to the formed Sor-Ce6 NPs. Our study demonstrates a promising self-assembled strategy for overcoming hypoxia-related PDT resistance for oral cancer treatment. • Carrier-free Sorafenib-Ce6 self-assemblies are designed by molecular simulation • The effect of oxygen-dependent PDT is boosted by inducing ferroptosis in oral cancer • Exogenous Fe3+ enhanced Sorafenib's ferroptosis inducing effect in oral cancer • Sor-Ce6 NPs is suitable for fluorescence and T 1 MR dual-modal imaging-guided PDT [Display omitted] [ABSTRACT FROM AUTHOR]

Nowadays, cancer has become the leading cause of death worldwide, driving the need for effective therapeutics to improve patient prognosis. Photodynamic therapy (PDT) has been widely applied as an antitumor modality, owing to its minimal invasiveness, localized tumor damage, and high safety profile. However, its efficacy is limited by poor stability of photosensitizers, inadequate tumor accumulation, and a complex tumor microenvironment. To overcome these challenges, extensive endeavors have been made to explore the co‐assembly of the widely used photosensitizer chlorin e6 (Ce6) with various functional small molecules to enhance pharmacodynamic activity. This review provides a comprehensive overview of current studies on Ce6‐based nanoparticles for effective PDT and precise delivery of functional molecules. The self‐assembly mechanism will be discussed in detail, with a focus on potential strategies for combinational therapy with PDT. [ABSTRACT FROM AUTHOR]

Rationally designed multiporphyrinic architectures for boosting photodynamic therapy (PDT) have attracted significant attentions recently years due to their great potential for light‐mediated generation of reactive oxygen species. However, there is still a gap between the structure design and their PDT performance for biomedical applications. This tutorial review provides a historical overview on (i) the basic concept of PDT for deeply understanding the porphyrin‐mediated PDT reactions, (ii) developing strategies for constructing porphyrinic architectures, like nanorings, boxes, metal‐organic frameworks (MOFs), covalent‐organic frameworks (COFs), vesicles, etc., where we classified into the following three categories: multiporphyrin arrays, porphyrinic frameworks, and others porphyrin assemblies, (iii) the various application scenarios for clinical cancer therapy and antibacterial infection. Also, the existing challenges and future perspectives on the innovation of porphyrinic architectures for clinical PDT applications are mentioned in the end section. Moreover, the porphyrinic nanomaterials with atomically precise architectures provide an ideal platform for investigating the relationship between structures and PDT outputs, design of personalized "all‐in‐one" theranostic agents, and the popularization and application in wider biomedical fields. [ABSTRACT FROM AUTHOR]

Cancer therapy, especially for tumors near sensitive areas, demands precise treatment. This review explores photodynamic therapy (PDT), a method leveraging photosensitizers (PS), specific wavelength light, and oxygen to target cancer effectively. Recent advancements affirm PDT’s efficacy, utilizing ROS generation to induce cancer cell death. With a history spanning over decades, PDT’s dynamic evolution has expanded its application across dermatology, oncology, and dentistry. This review aims to dissect PDT’s principles, from its inception to contemporary medical applications, highlighting its role in modern cancer treatment strategies.

Pathological scars (PS), including hypertrophic scars (HTS) and keloids, are a common complication of poor wound healing that significantly affects patients’ quality of life. Currently, there are several treatment options for PS, including surgery, drug therapy, radiation therapy, and biological therapy. However, these treatments still face major challenges such as low efficacy, high side effects, and a high risk of recurrence. Therefore, the search for safer and more effective treatments is particularly urgent. New materials often have less immune rejection, good histocompatibility, and can reduce secondary damage during treatment. New technology can also reduce the side effects of traditional treatments and the recurrence rate after treatment. Furthermore, derivative products of new materials and biomaterials can improve the therapeutic effect of new technologies on PS. Therefore, new technologies and innovative materials are considered better options for enhancing PS. This review concentrates on the use of two emerging technologies, microneedle (MN) and photodynamic therapy (PDT), and two novel materials, photosensitizers and exosomes (Exos), in the treatment of PS.

Actinic keratosis (AK) is characterized by a reddish or occasionally skin-toned rough patch on sun-damaged skin, and it is regarded as a precursor to squamous cell carcinoma (SCC). Photodynamic therapy (PDT), utilizing 5-aminolevulinic acid (ALA) along with red light, is a recognized treatment option for AK that is limited by the penetration depth of light and the distribution of the photosensitizer into the skin. Cold atmospheric plasma (CAP) is a partially ionized gas with permeability-enhancing and anti-cancer properties. This study analyzed, in vitro, whether a combined treatment of CAP and ALA-PDT may improve the efficacy of the treatment. In addition, the effect of the application sequence of ALA and CAP was investigated using in vitro assays and the molecular characterization of human oral SCC cell lines (SCC-9, SCC-15, SCC-111), human cutaneous SCC cell lines (SCL-1, SCL-2, A431), and normal human epidermal keratinocytes (HEKn). The anti-tumor effect was determined by migration, invasion, and apoptosis assays and supported the improved efficacy of ALA-PDT in combination with CAP. However, the application sequence ALA-CAP–red light seems to be more efficacious than CAP-ALA–red light, which is probably due to increased intracellular ROS levels when ALA is applied first, followed by CAP and red light treatment. Furthermore, the expression of apoptosis- and senescence-related molecules (caspase-3, -6, -9, p16INK4a, p21CIP1) was increased, and different genes of the junctional network (ZO-1, CX31, CLDN1, CTNNB1) were induced after the combined treatment of CAP plus ALA-PDT. HEKn, however, were much less affected than SCC cells. Overall, the results show that CAP may improve the anti-tumor effects of conventional ALA-PDT on SCC cells. Whether this combined application is successful in treating AK in vivo has to be carefully examined in follow-up studies.

Gliomas account for 24% of all the primary brain and Central Nervous System (CNS) tumors. These tumors are diverse in cellular origin, genetic profile, and morphology but collectively have one of the most dismal prognoses of all cancers. Work is constantly underway to discover a new effective form of glioma therapy. Photodynamic therapy (PDT) may be one of them. It involves the local or systemic application of a photosensitive compound—a photosensitizer (PS)—which accumulates in the affected tissues. Photosensitizer molecules absorb light of the appropriate wavelength, initiating the activation processes leading to the formation of reactive oxygen species and the selective destruction of inappropriate cells. Research focusing on the effective use of PDT in glioma therapy is already underway with promising results. In our work, we provide detailed insights into the molecular changes in glioma after photodynamic therapy. We describe a number of molecules that may contribute to the resistance of glioma cells to PDT, such as the adenosine triphosphate (ATP)-binding cassette efflux transporter G2, glutathione, ferrochelatase, heme oxygenase, and hypoxia-inducible factor 1. We identify molecular targets that can be used to improve the photosensitizer delivery to glioma cells, such as the epithelial growth factor receptor, neuropilin-1, low-density lipoprotein receptor, and neuropeptide Y receptors. We note that PDT can increase the expression of some molecules that reduce the effectiveness of therapy, such as Vascular endothelial growth factor (VEGF), glutamate, and nitric oxide. However, the scientific literature lacks clear data on the effects of PDT on many of the molecules described, and the available reports are often contradictory. In our work, we highlight the gaps in this knowledge and point to directions for further research that may enhance the efficacy of PDT in the treatment of glioma.

SARS-CoV-2 is a highly pathogenic virus responsible for the COVID-19 disease. It belongs to the Coronaviridae family, characterized by a phospholipid envelope, which is crucial for viral entry and replication in host cells. Hypericin, a lipophilic, naturally occurring photosensitizer, was reported to effectively inactivate enveloped viruses, including SARS-CoV-2, upon light irradiation. In addition to its photodynamic activity, Hyp was found to exert an antiviral action also in the dark. This study explores the mechanical properties of heat-inactivated SARS-CoV-2 viral particles using Atomic Force Microscopy (AFM). Results reveal a flexible structure under external stress, potentially contributing to the virus pathogenicity. Although the fixation protocol causes damage to some particles, correlation with fluorescence demonstrates colocalization of partially degraded virions with their genome. The impact of hypericin on the mechanical properties of the virus was assessed and found particularly relevant in dark conditions. These preliminary results suggest that hypericin can affect the mechanical properties of the viral envelope, an effect that warrants further investigation in the context of antiviral therapies.

The clinical application of photodynamic therapy (PDT) is hampered by the suboptimal tumor-targeting properties of photosensitizers (PSs) and the presence of abundant antioxidants in cancer cells. To overcome these limitations, in this study, we proposed a formulation of an Ir-(III) complex into a promising tumor-targeted coordination polymer (Ir-PB), which could self-assemble into nanoparticles (Ir-PB NPs) for bioimaging and tumor-targeted PDT. Ir-PB NPs were found to efficiently target A549 cells and specifically accumulate in the mitochondria. Under light irradiation (400 nm, 10 mW/cm2, 15 min), Ir-PB NPs could trigger cell death through a combination of apoptosis and ferroptosis pathways by the photoinduced depletion of nicotinamide adenine dinucleotide phosphate (NADPH) and glutathione (GSH) and the photoinduced production of single oxygen (1O2). The mechanisms featured the attenuation of the antioxidant capacity of tumor cells, the reduction of mitochondrial membrane potential (MMP), decrease in ATP production, activation of Caspase-3 protein, accumulation of lipid peroxidation (LPO), shrinkage of mitochondria, and down-regulation of glutathione peroxidase 4 (GPX4). The effectiveness of Ir-PB NPs in inhibiting tumor growth upon light irradiation was confirmed using an A549 xenograft mouse model. This study presents a promising strategy for developing photodynamic drugs that have excellent tumor-targeting abilities and enhance the efficiency of PDT. [ABSTRACT FROM AUTHOR]

[Display omitted] The two-step synthesis of porphyrin derivatives, exhaustively bbb-substituted at the 'Eastern half', starting from meso- tetraarylporphyrin chelates (Cuii, Znii, Niii) upon their reaction with nitric acid, is described. The intermediates obtained (mainly dinitro-derivatives) in the reaction with carbanions bearing a leaving group X at the reactive centre give tetrasubstituted at the bbb-positions products, the ones of vicarious nucleophilic substitution of hydrogen. The products seem to be potential anticancer PDT agents, practically unavailable by other methods. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a promising cancer treatment that kills cancer cells selectively by stimulating reactive oxygen species generation with photosensitizers exposed to specific light wavelengths. 5-aminolevulinic acid (5-ALA) is a widely used photosensitizer. However, its limited tumour penetration and targeting reduce its therapeutic efficacy. Scholars have investigated nano-delivery techniques to improve 5-ALA administration and efficacy in PDT. This review summarises recent advances in biological host biosynthetic pathways and regulatory mechanisms for 5-ALA production. The review also highlights the potential therapeutic efficacy of various 5-ALA nano-delivery modalities, such as nanoparticles, liposomes, and gels, in treating various cancers. Although promising, 5-ALA nano-delivery methods face challenges that could impair targeting and efficacy. To determine their safety and biocompatibility, extensive preclinical and clinical studies are required. This study highlights the potential of 5-ALA-NDSs to improve PDT for cancer treatment, as well as the need for additional research to overcome barriers and improve medical outcomes. [ABSTRACT FROM AUTHOR]

(1) Background: The protoporphyrin IX (PpIX)-mediated fluorescence-guided resection and interoperative photodynamic therapy (PDT) of remaining cells may be effective adjuvants to the resection of glioma. Both processes may be enhanced by increasing intracellular PpIX concentrations, which can be achieved through iron chelation. AP2-18 is a novel combinational drug, which ester-links a PpIX precursor (aminolaevulinic acid; ALA) to an iron-chelating agent (CP94). (2) Methods: Human glioma U-87 MG cells were cultured in 96-well plates for 24 h and incubated for 3 or 6 h with various test compound combinations: ALA (±) CP94, methyl aminolevulinate (MAL) (±) CP94 and AP2-18. PpIX fluorescence was measured at 0, 3 or 6 h with a Bio-tek Synergy HT plate reader, as well as immediately after irradiation with a 635 nm red light (Aktilite CL16 LED array), representing the PDT procedure. Cell viability post-irradiation was assessed using the neutral red assay. (3) Results: AP2-18 significantly increased PpIX fluorescence compared to all other test compounds. All treatment protocols effectively achieved PDT-induced cytotoxicity, with no significant difference between test compound combinations. (4) Conclusions: AP2-18 has potential to improve the efficacy of fluorescence-guided resection either with or without the subsequent intraoperative PDT of glioma. Future work should feature a more complex in vitro model of the glioma microenvironment. [ABSTRACT FROM AUTHOR]

Radical treatments and active surveillance are valid therapeutic approaches for low-risk prostate cancer. The oncologic effectiveness and morbidity of Radical Prostatectomy (RP) and radiotherapy have been broadly validated. Focal therapies pursue to reduce the morbidity observed after radical treatments, while preserving the oncologic effectiveness. This study aims to review the state-of-the-art about principles, oncologic effectiveness, morbidity, and side-effects associated with leading focal therapies. We review and summarize articles related with Cryotherapy, High-Intensity Focal Ultrasound (HIFU), Photodynamic Therapy (PDT), and Irreversible Electroporating (IRE) published in MEDLINE from 2000 to 2022. There is a wide heterogeneity in terms of the measurement of effectiveness and morbidity. Hence, comparing different energies, strategies and protocols seem to be unprecise and controversial. Cryosurgery and HIFU have reported more clinical experience than PDT and IRE. Biochemical recurrence rate after the first session varied from 4.5% to 23%, and up to 20% of patients underwent a salvage radical treatment. The reported incidence of erectile disfunction and urinary incontinence ranges from 3% to 50% and 0% to 34%, respectively. None randomized clinical trial comparing any focal therapy to any radical treatment has been published. We conclude that the expansion of focal therapies requires the consolidation of MRI-guided fusion biopsies in everyday clinical practice. Short-term oncologic effectiveness has been proved and supports their usefulness in low-risk patients unfit for surgical treatment. However, long-term effects and the clinical experience in intermediate and high-risk patients remains limited. Currently none of the focal therapies can be considered the Gold Standard for low-risk patients. [ABSTRACT FROM AUTHOR]

This in vitro study was conducted to evaluate the effects of blue light (λ = 420–480nm), titanium dioxide-decorated silver (TiO2/Ag) nanoparticles, and their combined application on the viability of A431 skin cancer cells. Cells cultured in a medium enriched with 10% fetal bovine serum were subjected to three distinct treatments: exposure to blue light, application of TiO2/Ag nanoparticles, and a combination of both. The MTT assay was utilized to determine cell viability post 24-hour incubation, with the resultant color intensity measured via a plate reader. Findings indicated a significant reduction in cell viability: blue light exposure led to an approximately 82% decrease at the 45-minute mark; nanoparticle treatment resulted in a notable viability reduction across all concentrations (p≤0.001); and the combined treatment displayed an enhanced effect, reducing cell viability by 42.79% relative to the control group after 45 minutes. Notably, the highest nanoparticle concentration (400 µg/ml) demonstrated superior anticancer efficacy. The synergistic impact of the combined treatment was evident, surpassing the individual effects of either blue light or TiO2/Ag nanoparticles in diminishing A431 cell numbers. This study underscores the potential of integrating photodynamic therapy (PDT) with nanoparticle technology in targeting skin cancer cells, highlighting a promising avenue for therapeutic intervention. [ABSTRACT FROM AUTHOR]

In this review, we delve into the realm of photodynamic therapy (PDT), an established method for combating cancer. The foundation of PDT lies in the activation of a photosensitizing agent using specific wavelengths of light, resulting in the generation of reactive oxygen species (ROS), notably singlet oxygen (1O2). We explore PDT's intricacies, emphasizing its precise targeting of cancer cells while sparing healthy tissue. We examine the pivotal role of singlet oxygen in initiating apoptosis and other cell death pathways, highlighting its potential for minimally invasive cancer treatment. Additionally, we delve into the complex interplay of cellular components, including catalase and NOX1, in defending cancer cells against PDT-induced oxidative and nitrative stress. We unveil an intriguing auto-amplifying mechanism involving secondary singlet oxygen production and catalase inactivation, offering promising avenues for enhancing PDT's effectiveness. In conclusion, our review unravels PDT's inner workings and underscores the importance of selective illumination and photosensitizer properties for achieving precision in cancer therapy. The exploration of cellular responses and interactions reveals opportunities for refining and optimizing PDT, which holds significant potential in the ongoing fight against cancer. [ABSTRACT FROM AUTHOR]

Objectives: Prostate cancer (PCa) is the most commonly diagnosed cancer and the second leading cause of cancer death in men in the USA. Photodynamic therapy (PDT) is a state-of-the-art treatment that combines high selectivity with minor side effects. Pheophorbide-a (Pheo) is a natural pigment with a photosensitizer property. Our study delved into the impact of Pheo alone or Pheo-PDT combination on the androgen-independent metastatic prostate cancer (AIPC) cell lines DU-145 and C4-2. Furthermore, an in-depth examination has been conducted on the photocytotoxicity mechanism of Pheo-PDT in these specific cell lines. Methods: In vitro studies were conducted using the AIPC cell lines. DU-145 and C4-2 cells were treated with Pheo at different concentrations for 60 min alone, or Pheo treatment followed by exposure to 670 nm illumination (60 mW/cm2 in 88 s pulses), producing 5 J/cm2 via portable light-emitting diode. Key findings: Our results show that Pheo-PDT substantially inhibits cell viability, anchorage-independent growth, and migration capacities and induces autophagy and apoptosis via the over-production of reactive oxygen species that mediates endoplasmic reticulum stress in AIPC cell lines. Conclusions: Our study highlights the potential benefits of Pheo-PDT in metastatic hormone-insensitive PCa cell lines. It paves the way for treating localized and locally advanced PCa as a possible candidate for castration-resistant prostate cancer. Graphical Abstract [ABSTRACT FROM AUTHOR]