Mechanism Of Photodynamic Therapy Research Articles

Modulation of heat shock protein expression and cytokine levels in MCF-7 cells through photodynamic therapy.

In this study, we assess the impact of photodynamic therapy (PDT) using aluminum phthalocyanine tetrasulfonate (AlPcS4) on the viability and cellular stress responses of MCF-7 breast cancer cells. Specifically, we investigate changes in cell viability, cytokine production, and the expression of stress-related genes. Experimental groups included control cells, those treated with AlPcS4 only, light-emitting diode (LED) only, and combined PDT. To evaluate these effects on cell viability, cytokine production, and the expression of stress-related genes, techniques such as 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, enzyme-linked immunosorbent assays (ELISA), and real-time quantitative PCR (RT‒qPCR) were employed. Our findings reveal how PDT with AlPcS4 modulates mitochondrial activity and cytokine responses, shedding light on the cellular pathways essential for cell survival and stress adaptation. This work enhances our understanding of PDT's therapeutic potential and mechanisms in treating breast cancer.

Photodynamic therapy inhibits cancer progression and induces ferroptosis and apoptosis by targeting P53/GPX4/SLC7A11 signaling pathways in cholangiocarcinoma

BackgroundCholangiocarcinoma (CCA) is a malignant tumor with a poor prognosis. The specific mechanism of photodynamic therapy (PDT) in treating CCA remains unclear. This study aims to investigate the mechanisms of PDT in the treatment of CCA and try to improve the therapeutic effect of PDT by intervening associated signaling pathways. MethodsThe Cell Counting Kit-8 (CCK-8) was used to examine the cytotoxicity of CCA cell lines following PDT. Apoptosis and reactive oxygen species (ROS) levels were measured by flow cytometry. A transmission electron microscope was used to study the changes in cell mitochondria after PDT. The levels of glutathione (GSH), malondialdehyde (MDA), ferrous iron (Fe2+), lactate dehydrogenase (LDH), and lipid peroxide (LPO) were determined. Changes in the expression of apoptosis and ferroptosis-related proteins were determined using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Xenograft tumor models were developed to investigate the effects of PDT on tumor proliferation, apoptosis, and ferroptosis in vivo. ResultsPDT inhibited tumor proliferation and induced apoptosis both in vivo and in vitro. This treatment led to swelling and damage of the mitochondria in affected cells. Furthermore, ROS levels rose, accompanied by an increase in the proportion of apoptotic-positive cells. The expressions of Bax and Caspase-3 were upregulated, while the Bcl-2 was downregulated. Meanwhile, PDT triggered ferroptosis, marked by decreased expressions of GPX4 and SLC7A11, and reduced GSH levels. This was accompanied by upregulation of P53 expression and heightened levels of Fe2+, LPO, MDA, and LDH. After inducing the ferroptosis pathway, the therapeutic effect of PDT was enhanced, the tumor tissue was further reduced, and the degree of malignancy was reduced. ConclusionPDT promotes apoptosis and ferroptosis of cholangiocarcinoma cells by activating the P53/SLC7A11/GPX4 signaling pathway and inhibits the growth of cholangiocarcinoma. Inducing ferroptosis can enhance the effectiveness of photodynamic therapy.

The effects of photodynamic therapy on the immune response of women with cervical high-grade squamous intraepithelial lesions

ObjectiveTo evaluate and elucidate the effects and mechanism of photodynamic therapy (PDT) on the immune response of women with cervical high-grade squamous intraepithelial lesions (HSILs). Materials and methodsImmunofluorescence staining was used to compare immune infiltration before and after PDT in 23 patients with cervical HSILs. The infiltration of immune cells into the cervical tissues of patients with different outcomes was also compared at the 6-month follow-up period. Immune cell counts in samples collected before and after treatment were compared. ResultsWe found an increased number of CD8+ T cell infiltration, an increased proportion of CD8+ T cells expressing Granzyme B (GrB), Chemokine receptor 3 (CXCR3), and CD8+ tissue-resident memory T (TRM) cells, and a decreased proportion of CD8+ T cells expressing PD-1 in patients with cervical HSIL compared to that before PDT. Moreover, at the 6-month follow-up, there was higher infiltration of CD8+ T and CD8+ TRM cells, higher expression of GrB and CXCR3, and lower expression of PD-1 on CD8+ T cells in the HPV and cervical HSIL clearance groups than in the persistent HPV infection and cervical HSIL regression groups. However, no significant difference was observed in the number of CD8+ TSCM following PDT. ConclusionPDT activates immune responses mediated by CD8+ T cells. The degree of the immune response is correlated with the prognosis of cervical HSIL.

Identification of Ru-based PDT resistance mechanisms by CRISPR/Cas9 screen in HNSCC

SignificanceThis project provides an in-depth knowledge of the mode of action of novel designed Ruthenium photodynamic therapy (PDT) complex, and provides information about how head and neck squamous cell carcinomas (HNSCC) cells resist to these treatments. ApproachTo obtain a comprehensive view of the molecular bases of Ru-based photocytotoxicity in HNSCC, we performed a genome-wide randomly knock-out clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 screen. The comparison of sequencing data from treated and non-treated conditions will identify deleted sequences in challenged SQ20B cells by next-generation sequencing (NGS). ResultsWe have identified HSPE1 gene is associated to resistance mechanisms induced by RuII-based PDT treatment. Further investigation of the candidate gene on apoptosis induction through gain- and loss- of function assays. ConclusionsIn this study, we employed a genome-wide CRISPR/Cas9 screen to decipher molecular response mechanisms of Ru-based PDT in HNSCC cells.

Oxygen-independent organic photosensitizer with ultralow-power NIR photoexcitation for tumor-specific photodynamic therapy

Photodynamic therapy (PDT) is a promising cancer treatment but has limitations due to its dependence on oxygen and high-power-density photoexcitation. Here, we report polymer-based organic photosensitizers (PSs) through rational PS skeleton design and precise side-chain engineering to generate •O2− and •OH under oxygen-free conditions using ultralow-power 808 nm photoexcitation for tumor-specific photodynamic ablation. The designed organic PS skeletons can generate electron-hole pairs to sensitize H2O into •O2− and •OH under oxygen-free conditions with 808 nm photoexcitation, achieving NIR-photoexcited and oxygen-independent •O2− and •OH production. Further, compared with commonly used alkyl side chains, glycol oligomer as the PS side chain mitigates electron-hole recombination and offers more H2O molecules around the electron-hole pairs generated from the hydrophobic PS skeletons, which can yield 4-fold stronger •O2− and •OH production, thus allowing an ultralow-power photoexcitation to yield high PDT effect. Finally, the feasibility of developing activatable PSs for tumor-specific photodynamic therapy in female mice is further demonstrated under 808 nm irradiation with an ultralow-power of 15 mW cm−2. The study not only provides further insights into the PDT mechanism but also offers a general design guideline to develop an oxygen-independent organic PS using ultralow-power NIR photoexcitation for tumor-specific PDT.

Near-infrared light-activated smart nanogels for remotely controlled cytochrome c release and photodynamic therapy

The utilization of reactive oxygen species (ROS) generated through photodynamic therapy (PDT) for remote-controlled release of protein drugs at specific sites using near-infrared light represents a groundbreaking development in protein delivery system innovation. To illustrate this principle, we engineered near-infrared light-activated smart nanogels (NASNs) by chemically cross-linking ROS-responsive linkages within hyaluronic acid-graft-methoxy poly(ethylene glycol)-diethylenetriamine-grafted-chlorine e6 (Ce6) polymer (HA-PEG-Dien-g-Ce6) and carboxylated thioketal (TK) serving as a cross-linker to enable PDT-driven cytochrome c (CC) liberation. The NASNs demonstrated substantial loading capacity and exceptional stability across diverse biological settings, attributed to the robust nature of the TK bond. Notably, CC-loaded NASNs effectively penetrated A549 cells via CD44-mediated endocytosis and rapidly escaped from the endo-lysosomal compartment. Upon light activation, the Ce6 produced ROS, leading to TK bond disruption in NASNs, and consequent release of encapsulated CC. This precise, photo-induced PDT mechanism and CC liberation markedly enhanced antitumor efficacy while maintaining minimal toxicity, establishing a solid foundation for remote, as-needed protein delivery systems and potential integration with additional therapeutic modalities.

Mitochondria-targeted photodynamic therapy triggers GSDME-mediated pyroptosis and sensitizes anti-PD-1 therapy in colorectal cancer

BackgroundThe effectiveness of immune checkpoint inhibitors in colorectal cancer (CRC) is limited due to the low tumor neoantigen load and low immune infiltration in most microsatellite-stable (MSS) tumors. This study...

Exploration of new models for primary dysmenorrhea treatment: low-power visible-light-activated photodynamic therapy and oral contraceptives.

Primary dysmenorrhea (PD) is one of the most common reasons that affect the life quality of women during childbearing age. This research aims to explore the efficacy and curative effect characteristics of oral contraceptives and low-power visible-light-activated photodynamic therapy (PDT). Besides investigating the possible mechanism of PDT, we expected to find a treatment model with better efficacy and fewer side effects. It was a multicenter, randomized, parallel-controlled study. Eligible participants were randomly assigned to three groups: placebo group, oral contraceptive (Marvelon) group, and the PDT group. They were treated continuously for three menstrual cycles and followed up for two cycles after treatment. The scores of the visual analog scale (VAS) and the concentration of pain-related small molecules in blood before and after treatment were recorded in each group, which can evaluate the therapeutic characteristics of different treatments. Both Marvelon and PDT were effective. The effect of Marvelon appears quickly which can significantly relieve symptoms at the beginning, while PDT shows a relatively slow role. There was no significant difference in the final efficacy two cycles after treatment. The therapeutic effect was achieved by reducing the concentrations of prostaglandin 2 (PGE2) and endothelin (ET) in the blood. Marvelon and PDT are effective methods for the treatment of PD. The long-term efficacy of the two is similar, while the therapeutic characteristics and the side effects are different. Patients can choose the suitable way according to their individual needs.

Rational design of type-I photosensitizer molecules for mitochondrion-targeted photodynamic therapy.

Photodynamic therapy (PDT) has emerged as a promising approach for tumor treatment. However, traditional type II PDT faces limitations due to its oxygen-dependent nature. Type-I photosensitizers (PSs) exhibit superiority over conventional type-II PSs owing to their diminished oxygen dependence. Nevertheless, designing effective type-I PSs remains a significant challenge. In this work, we provide a novel strategy to tune the PDT mechanism of an excited photosensitizer through aryl substituent engineering. Using S-rhodamine as the base structure, three PSs were synthesized by incorporating phenyl, furyl, or thienyl groups at the meso position. Interestingly, furyl- or thienyl-substituted S-rhodamine are type-I-dominated PSs that produce O2˙-, while phenyl S-rhodamine results in O2˙- and 1O2 through type-I and type-II mechanisms, respectively. Experimental analyses and theoretical calculations showed that the introduction of a five-membered heterocycle at the meso position promoted intersystem crossing (ISC) and electron transfer, facilitating the production of O2˙-. Furthermore, furyl- or thienyl-substituted S-rhodamine exhibited high phototoxicity at ultralow concentrations. Thienyl-substituted S-rhodamine showed promising PDT efficacy against hypoxic solid tumors. This innovative strategy provides an alternative approach to developing new type-I PSs without the necessity for creating entirely new skeletons.

Transvascular delivery of talaporfin sodium to subcutaneous tumors in mice by nanosecond pulsed laser-induced photomechanical waves

BackgroundWe previously developed a site-specific transvascular drug delivery system (DDS) based on photomechanical waves (PMWs) or laser-induced stress/shock waves (LISWs). In this study, we investigated the validity of this method to deliver a clinical photosensitizer, talaporfin sodium (TS), to subcutaneous tumors in mice and to enhance the efficacy of photodynamic therapy (PDT). MethodsTS solution (2.5 mg/kg) was intravenously injected into mice. Immediately thereafter, PMWs were applied to the tumor by irradiating a laser target with a Q-switched ruby laser pulse (0.8 J/cm2). Five hours after TS administration, some tumors were excised to evaluate the depth distribution of the delivered TS under a fluorescence microscope. Other tumors were subjected to PDT by irradiating the tissues with a 665 nm continuous-wave laser diode (75 mW/cm2, 667 s) at this timepoint. The effects of PDT were evaluated on the basis of the two primary therapeutic mechanisms of TS-mediated PDT: i) damage to tumor cells and ii) damage to endothelial cells of tumor vessels, i.e., the vascular shutdown effect on tumors. ResultsPMW application significantly increased the accumulation of TS in the tumor parenchyma but not in the tumor vessel walls; the endothelial cell junctions of tumor vessels should be the route of TS delivery enhanced by PMWs. Thus, as a result of PMW application followed by PDT, while the vascular shutdown effect on the tumors was not enhanced, direct damage to the tumor cells was increased, resulting in significant tumor growth retardation without body weight loss for 7 days after treatment.

Ru(II)-Cyanine Complexes as Promising Photodynamic Photosensitizers for the Treatment of Hypoxic Tumours with Highly Penetrating 770 nm Near-Infrared Light.

Light-activated treatments, such as photodynamic therapy (PDT), provide temporal and spatial control over a specific cytotoxic response by exploiting toxicity differences between irradiated and dark conditions. In this work, a novel strategy for developing near infrared (NIR)-activatable Ru(II) polypyridyl-based photosensitizers (PSs) was successfully developed through the incorporation of symmetric heptamethine cyanine dyes in the metal complex via a phenanthrimidazole ligand. Owing to their strong absorption in the NIR region, the PSs could be efficiently photoactivated with highly penetrating NIR light (770 nm), leading to high photocytotoxicities towards several cancer cell lines under both normoxic and hypoxic conditions. Notably, our lead PS (Ru-Cyn-1), which accumulated in the mitochondria, exhibited a good photocytotoxic activity under challenging low-oxygen concentration (2% O2) upon NIR light irradiation conditions (770 nm), owing to a combination of types I and II PDT mechanism. The fact that the PS Protoporphyrin IX (PpIX), the metabolite of the clinically approved 5-ALA PS, was found inactive under the same challenging conditions positions Ru-Cyn-1 complex as a promising PDT agent for the treatment of deep-seated hypoxic tumours.

Short term choroidal microvascular changes following photodynamic therapy in chronic central serous chorioretinopathy

BackgroundCentral serous chorioretinopathy (CSC) is characterized by focal serous detachment of the retina, primarily affecting the macula. Photodynamic therapy (PDT) is the best choice for treatment of chronic and recurrent patients. In this study we aim to evaluate the early effects of the half dose protocol (3 mg/m2 verteporfine) of PDT laser treatment on the micro vasculature of choroid. MethodsAmong thirty-one patients (62 eyes), twenty eyes were in the control group and forty-two eyes received PDT laser treatment. Vision log MAR, CMT (central macular thickness), SRF (sub retinal fluid), BCT (baseline choroidal thickness), CVI (choroidal vascular index), and laser treated area were compared between two groups. ResultsResults show that no strong correlation was detected between the impact of laser treatment and resolution of SRF in the first week in the fovea. The mean best corrected visual acuity (BCVA) of the patients significantly increased from 20/63 at the beginning of the study, according to the Snellen chart, to 20/49 in the first week and 20/38 in the sixth week. PDT can significantly reduce SRF and CMT in 6 weeks compared to the control group. Although there was initially a small, non-statistically significant increase in choroidal thickness and CVI after 1 week, a dramatic decrease occurs after 6 weeks. Therefore, after 6 weeks of PDT laser, all the indicators such as SRF, CMT, choroidal thickness, and CVI significantly reduced. ConclusionPDT laser can significantly reduce SRF and CMT at 1 and 6 weeks and choroidal thickness and CVI at 6 weeks in chronic CSC patients. Also, a larger laser treated area has no impact on the final outcome. Therefore, it seems that the mechanism of PDT in CSC disease is the recovery of choriocapillaris circulation.

Intratibial osteosarcoma growth and pulmonary metastasis inhibition by HIPPO signaling pathway-induced photodynamic therapy

Cancer is a global leading cause of death, with nearly 10 million people dying from cancer in 2020. Photodynamic therapy (PDT) has emerged as a promising cancer treatment modality; however, the potential molecular mechanisms remain obscure. Herein, we designed a near-infrared (NIR) light-activated nanoplatform (TPBC-PEG) to explore the therapeutic effects and mechanisms of PDT by using a model of intratibial primary and pulmonary metastasis osteosarcoma. Under laser irradiation, TPBC-PEG photosensitizer dose-dependently inhibited proliferative and metastatic capabilities while promoting apoptosis of osteosarcoma cells in vitro, and also effectively suppressed carcinogenesis and pulmonary metastasis in osteosarcoma xenograft mouse model. Moreover, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis after high-throughput mRNA-seq indicated that the HIPPO signaling pathway was one of the 20 most significantly related signaling pathways. And a series of experiments for determining the HIPPO signaling activity were conducted to reconfirm the specificity. Collectively, PDT of TPBC-PEG micelles against carcinogenesis and pulmonary metastasis of deep-seated intratibial osteosarcoma was achieved by activating HIPPO signaling pathway. Our study identified a hitherto uncharacterized molecular mechanism of PDT, which may provide new insights to understand and design promising nanoplatforms for future cancer therapies.

Molybdenum-oxo-sulfide quantum dot-based nanocarrier: Efficient generation of reactive oxygen species via photo/chemodynamic therapy and stimulus-induced drug release

The fabrication of multifunctional nano-therapies has increased gradually to strengthen the therapeutic performance and minimize adverse effects of traditional cancer treatment strategies. Currently, we have designed a facile preparation drug-loaded nanocarrier for multimodal cancer therapy upon external stimuli. First, defect-rich molybdenum oxo-sulfide (MoOxS2-x) quantum dots (QDs) was synthesized via rapid biomineralization techniques with superior optical quantum yield reaching upto 37.28%. The presence of the Fenton ion, Mo+IV/+VI, enables MoOxS2-x QDs to efficiently catalyze peroxide solutions to produce •OH radicals for chemodynamic treatment (CDT) and also deactivate the intracellular glutathione (GSH) enzymes through redox reaction for boosted reactive oxygen species (ROS)-mediated therapies. In addition, upon laser combination, MoOxS2-x QDs generate ROS for photodynamic therapy (PDT). Also, due to a large amount of sulfide content, MoOxS2-x QDs showed excellent H2S gas release in acidic pH for cancer gas therapy. Then, MoOxS2-x QDs was further conjugated with ROS-responsive thioketal linked Camptothecin (CPT-TK-COOH) drug, forming a multitargeted MoOxS2-xCPT anticancer agent with better drug-loading efficiency (38.8%). After triggering the ROS generation through the CDT and PDT mechanisms, the thioketal linkage was disrupted, releasing up to 79% of the CPT drug in 48 h. Besides, in vitro experiments verified that MoOxS2-x QDs possess higher biocompatibility with 4T1 and HeLa cells but also showed considerable toxicity in the presence of laser/H2O2, resulting in 84.45% cell death through PDT/CDT and chemotherapeutic effects. Therefore, the designed MoOxS2-xCPT exhibited outstanding therapeutic benefits for image-guided cancer therapy.

Wider indications and more efficient drug delivery: A bibliometric analysis and visualization of photodynamic therapy in skin cancer.

Photodynamic therapy (PDT) has been widely accepted in keratocyte carcinoma and an increasing number of literatures concerning PDT in skin cancer is published. But a detailed examination of publication patterns of PDT in skin cancer has not yet been carried out. Bibliographies were retrieved from Web of Science Core Collection restricted the publication date from January 1, 1985 to December 31, 2021. The search terms were photodynamic therapy and skin cancer. Visualization analysis and statistical analysis were performed by VOSviewer (Version 1.6.13), R software (Version 4.1.2) and Scimago Graphica (Version 1.0.15). 3248 documents were selected for analysis. The results showed that the number of annual publications related to PDT in skin cancer was gradually increased and would continue to increase in the future. The results illustrated that "melanoma", "nanoparticles", "drug-delivery", "mechanism", "delivery" and "in-vitro" are newly occurred topics. The most prolific country was the United States and the most productive institution was the University of Sao Paulo in Brazil. German researcher Szeimies RM published the most papers related to PDT in skin cancer. British Journal of Dermatology was the most popular journal in this field. The topic that PDT in skin cancer is a heated issue. Our study revealed the bibliometric result of the field, which might provide the prospects for further research. We recommend future investigations focusing on PDT in treating melanoma, innovation of photosensitizer, improvement of drug delivery and the mechanism of PDT in skin cancer.

Type Ι Photosensitizer Targeting G-Quadruplex RNA Elicits Augmented Immunity for Cancer Ablation.

Type Ι photodynamic therapy (PDT) represents a promising treatment modality for tumors with intrinsic hypoxia. However, type Ι photosensitizers (PSs), especially ones with near infrared (NIR) absorption, are limited and their efficacy needs improvement via new targeting tactics. We develop a NIR type Ι PS by engineering acridinium derived donor-π-acceptor systems. The PS exhibits an exclusive type Ι PDT mechanism due to effective intersystem crossing and disfavored energy transfer to O2 , and shows selective binding to G-quadruplexes (G4s) via hydrogen bonds identified by a molecular docking study. Moreover, it enables fluorogenic detection of G4s and efficient O2 ⋅- production in hypoxic conditions, leading to immunogenic cell death and substantial variations of gene expression in RNA sequencing. Our strategy demonstrates augmented antitumor immunity for effective ablation of immunogenic cold tumor, highlighting its potential of RNA-targeted type Ι PDT in precision cancer therapy.

Type I Photosensitizer Targeting G‐Quadruplex RNA Elicits Augmented Immunity for Cancer Ablation

AbstractType I photodynamic therapy (PDT) represents a promising treatment modality for tumors with intrinsic hypoxia. However, type I photosensitizers (PSs), especially ones with near infrared (NIR) absorption, are limited and their efficacy needs improvement via new targeting tactics. We develop a NIR type I PS by engineering acridinium derived donor‐π‐acceptor systems. The PS exhibits an exclusive type I PDT mechanism due to effective intersystem crossing and disfavored energy transfer to O2, and shows selective binding to G‐quadruplexes (G4s) via hydrogen bonds identified by a molecular docking study. Moreover, it enables fluorogenic detection of G4s and efficient O2⋅− production in hypoxic conditions, leading to immunogenic cell death and substantial variations of gene expression in RNA sequencing. Our strategy demonstrates augmented antitumor immunity for effective ablation of immunogenic cold tumor, highlighting its potential of RNA‐targeted type I PDT in precision cancer therapy.

Cell membrane biomimetic nanomedicines for cancer phototherapy

AbstractPhototherapy, mainly including photothermal therapy (PTT) and photodynamic therapy (PDT), can kill cancer cells by generating heat or reactive oxygen species, which has the advantages of being minimally invasive, high efficiency, and low toxicity. However, traditional phototherapeutic agents face challenges such as poor tumor targeting, susceptibility to passive immune clearance, and suboptimal biocompatibility, which limit their clinical application. Recently, cell membrane biomimetic technology endows phototherapeutic agents with unique biological functions, such as promoted immune escape, prolonged in vivo circulation time, improved biocompatibility, and enhanced anti‐tumor efficacy. In addition, phototherapy mediated by cancer cell membrane (CCM) or immune cell membrane‐modified phototherapeutic agents can promote broad anti‐tumor immunity. In this review, we deeply analyze the mechanisms of PTT and PDT, systematically discuss the synthesis strategies and biological functions of cell membrane biomimetic nanomaterials, and focus on the progress of phototherapy based on biomimetic nanomaterials and synergistic therapies such as chemotherapy, radiotherapy, immunotherapy, and sonodynamic therapy. Finally, we address the opportunities and future prospects of biomimetic nanomaterials in the field of cancer phototherapy. This comprehensive review is expected to provide insights into promoting the clinical translation of biomimetic phototherapeutic agents.

Global Trends and Research Progress of Photodynamic Therapy in Skin Cancer: A Bibliometric Analysis and Literature Review.

Based on photochemical reactions through the combined use of light and photosensitizers, photodynamic therapy (PDT) is gaining popularity for the treatment of skin cancer. Various photosensitizers and treatment regimens are continuously being developed for enhancing the efficacy of PDT on skin cancer. Reviewing the development history of PDT on skin cancer, and summarizing its development direction and research status, is conducive to the further research. To evaluate the research trends and map knowledge structure, all publications covering PDT on skin cancer were retrieved and extracted from Web of Science database. We applied VOSviewer and CiteSpace softwares to evaluate and visualize the countries, institutes, authors, keywords and research trends. Literature review was performed for the analysis of the research status of PDT on skin cancer. A total of 2662 publications were identified. The elements, mechanism, pros and cons, representative molecular photosensitizers, current challenges and research progress of PDT on skin cancer were reviewed and summarized. This study provides a comprehensive display of the field of PDT on skin cancer, which will help researchers further explore the mechanism and application of PDT more effectively and intuitively.

Chlorin e6-induced photodynamic effect facilitates immunogenic cell death of lung cancer as a result of oxidative endoplasmic reticulum stress and DNA damage

Suppression of the immune microenvironment is an important endogenous contributor to treatment failure in lung cancer. Photodynamic therapy (PDT) is widely used in the treatment of malignant tumors owing to its photo-selectivity and minimal side effects. Some studies have shown the ability of photodynamic action not only to cause photo-cytotoxicity to tumor cells but also to induce immunogenic cell death (ICD). However, the mechanism by which PDT enhances tumor immunogenicity is poorly understood. The present study aimed to explore the immunogenicity effect of PDT on lung cancer and to reveal the underlying mechanism. First, we searched for effective conditions for PDT-induced apoptosis in lung cancer cells. Just as expected, chlorin e6 (Ce6) PDT could enhance the immunogenicity of lung cancer cells alongside the induction of apoptosis, characterized by up-regulation of CRT, HSP90, HMGB1 and MHC-I. Further results showed the generation of ROS by Ce6 PDT under the above conditions, which is an oxidative damaging agent. Simultaneously, PDT induced endoplasmic reticulum (ER) stress in cells, as evidenced by enhanced Tht staining and up-regulated CHOP and GRP78 expression. Moreover, PDT led to DNA damage response (DDR) as well. However, the redox inhibitor NAC abolished the ER stress and DDR caused by PDT. More importantly, NAC also attenuated PDT-induced improvement of immunogenicity in lung cancer. On this basis, the PDT-induced CRT up-regulation was found to be attenuated in response to inhibition of ER stress. In addition, PDT-induced increase in HMGB1 and HSP90 release was blocked by inhibition of DDR. In summary, Ce6 PDT could produce ROS under certain conditions, which leads to ER stress that promotes CRT translocation to the cell membrane, and the resulting DNA damage causes the expression and release of nuclear HMGB1 and HSP90, thereby enhancing the immunogenicity of lung cancer. This current study elucidates the mechanism of PDT in ameliorating the immunogenicity of lung cancer, providing a rationale for PDT in regulating the immune microenvironment for the treatment of malignant tumors.