Targeting Photodynamic Therapy Research Articles

Photodynamic Therapy of Atherosclerotic Plaque Monitored by T1 and T2 Relaxation Times of Magnetic Resonance Imaging

Atherosclerosis, marked by plaque accumulation within arteries, results from lipid dysregulation, inflammation, and vascular remodeling. Plaque composition, including lipid-rich cores and fibrous caps, determines stability and vulnerability. Photodynamic therapy (PDT) has emerged as a promising treatment, leveraging photosensitizers to induce localized cytotoxicity upon light activation. PDT targets plaque components selectively, reducing burden and inflammation. Challenges remain in optimizing PDT parameters and translating preclinical success to clinical efficacy. Nonetheless, PDT offers a minimally invasive strategy for atherosclerosis management, promising personalized interventions for cardiovascular health. The objective of the current study was to present the findings from quantitative non-contrast MRI of atherosclerosis post-PDT by assessing relaxation times. The study aimed to utilize and optimize a 1.5T MRI system. Clinical scanners were used for MRI examinations. The research involved analyzing T1 and T2 relaxation times. Following treatment of the samples with Rose Bengal and exposure to pure oxygen, PDT irradiation was administered. The results indicated that the therapy impacted the crus, evidenced by a significant decrease in relaxation times in the MRI data.

Endoplasmic Reticulum-Targeting Self-Assembly Nanosheets Promote Autophagy and Regulate Immunosuppressive Tumor Microenvironment for Efficient Photodynamic Immunotherapy.

The poor efficiency and low immunogenicity of photodynamic therapy (PDT), and the immunosuppressive tumor microenvironment (ITM) lead to tumor recurrence and metastasis. In this work, TCPP-TER-Zn@RSV nanosheets (TZR NSs) that co-assembled from the endoplasmic reticulum (ER)-targeting photosensitizer TCPP-TER-Zn nanosheets (TZ NSs for short) and the autophagy promoting and indoleamine-(2, 3)-dioxygenase (IDO) inhibitor-like resveratrol (RSV) are fabricated to enhance antitumor PDT. TZR NSs exhibit improved therapeutic efficiency and amplified immunogenic cancer cell death (ICD) by ER targeting PDT and ER autophagy promotion. TZR NSs reversed the ITM with an increase of CD8+ T cells and reduce of immunosuppressive Foxp3 regulatory T cells, which effectively burst antitumor immunity thus clearing residual tumor cells. The ER-targeting TZR NSs developed in this paper presents a simple but valuable reference for high-efficiency tumor photodynamic immunotherapy.

Uridine-Modified Ruthenium(II) Complex as Lysosomal LIMP-2 Targeting Photodynamic Therapy Photosensitizer for the Treatment of Triple-Negative Breast Cancer.

Lysosome-targeted photodynamic therapy, which enhances reactive oxygen species (ROS)-responsive tumor cell death, has emerged as a promising strategy for cancer treatment. Herein, a uridine (dU)-modified Ru(II) complex (RdU) was synthesized by click chemistry. It was found that RdU exhibits impressive photo-induced inhibition against the growth of triple-negative breast cancer (TNBC) cells in normoxic and hypoxic microenvironments through ROS production. It was further revealed that RdU induces ferroptosis of MDA-MB-231 cells under light irradiation (650 nm, 300 mW/cm2). Additional experiments showed that RdU binds to lysosomal integral membrane protein 2 (LIMP-2), which was confirmed by the fact that RdU selectively localizes in the lysosomes of MDA-MB-231 cells and significantly augments the levels of LIMP-2. Molecular docking simulations and an isothermal titration calorimetry assay also showed that RdU has a high affinity to LIMP-2. Finally, in vivo studies in tumor-bearing (MDA-MB-231 cells) nude mice showed that RdU exerts promising photodynamic therapeutic effects on TNBC tumors. In summary, the uridine-modified Ru(II) complex has been developed as a potential LIMP-2 targeting agent for TNBC treatment through enhancing ROS production and promoting ferroptosis.

Assessment of the Response of Human Umbilical Vein Endothelial Cells to Photodynamic Therapy: Highlighting the Role of Il-17 Signaling Pathway.

Introduction: Photodynamic therapy (PDT) is a method based on the application of a photosensitive agent and the administration of light irradiation on the treated samples. PDT is applied as an effective tool with minimal side effects against tumor tissues. This study aimed to assess the targets of critical genes by PDT at the cellular level of cancer to provide a new perspective on its molecular mechanism. Methods: To assess the effect of PDT, we extracted the differentially expressed genes (DEGs) from the gene expression profiles of human umbilical vein endothelial cells (HUVECs) treated with PDT from Gene Expression Omnibus (GEO) databases. The queried DEGs were evaluated via a regulatory network and gene ontology enrichment to find the critical targets. Results: Among 76 queried significant DEGs, 27 individuals were interacted by activation, inhibition, and co-expression actions. Thirty DEGs were related to the five classes of biological terms. The IL-17 signaling pathway and PTGS2, CXCL8, FOS, JUN, CXCL1, ZFP36, and FOSB were identified as the crucial targets of PDT. Conclusion: PDT as a stimulator of gene expression and an activator of gene activity overexpressed and hyper-activated many genes. It seems that PDT introduces a number of genes and pathways that can be regulated by anticancer drugs to fight against cancers.

Photodynamic therapy for treatment of recurrent hemoptysis secondary to pulmonary endometriosis: a case report.

Pulmonary endometriosis (PEM) is rare, and drug therapy remains the primary treatment. However, patients with PEM frequently experience recurrent hemoptysis that is refractory to pharmacological intervention. We herein describe a patient with PEM who developed recurrent hemoptysis and was successfully treated with photodynamic therapy (PDT) after drug withdrawal. The patient was admitted to our hospital because of recurrent hemoptysis despite repeated drug treatments for more than 1 year. Given that PDT targets specific tissues and destroys vascular endothelial cells through the cytotoxic effect produced by the photodynamic reaction of the photosensitizer, we considered that it may effectively control hemoptysis secondary to vascular morphological changes in PEM. Therefore, we performed PDT in this case, and the patient's recurrent hemoptysis regressed. Approximately 2 years following PDT, the patient had recovered well and reported no discomfort. We recommend consideration of PDT as a treatment option for patients with PEM who develop recurrent hemoptysis after drug withdrawal. Notably, the patient's lung lesions should be superficial and limited, and no contraindications should be present.

A Versatile Theranostic Nanoplatform with Aggregation-Induced Emission Properties: Fluorescence Monitoring, Cellular Organelle Targeting, and Image-Guided Photodynamic Therapy.

Photosensitizers (PSs) play a key role in the photodynamic therapy (PDT) of tumors. However, commonly used PSs are prone to intrinsic fluorescence aggregation-caused quenching and photobleaching; this drawback severely limits the clinical application of PDT, necessitating new phototheranostic agents. Herein, a multifunctional theranostic nanoplatform (named TTCBTA NP) is designed and constructed to achieve fluorescence monitoring, lysosome-specific targeting, and image-guided PDT. TTCBTA with a twisted conformation and D-A structure is encapsulated in amphiphilic Pluronic F127 to form nanoparticles (NPs) in ultrapure water. The NPs exhibit biocompatibility, high stability, strong near-infrared emission, and desirable reactive oxygen species (ROSs) production capacity. The TTCBTA NPs also show high-efficiency photo-damage, negligible dark toxicity, excellent fluorescent tracing, and high accumulation in lysosome for tumor cells. Furthermore, TTCBTA NPs are used to obtain fluorescence images with good resolution of MCF-7 tumors in xenografted BALB/c nude mice. Crucially, TTCBTA NPs present a strong tumor ablation ability and image-guided PDT effect by generating abundant ROSs upon laser irradiation. These results demonstrate that the TTCBTA NP theranostic nanoplatform may enable highly efficient near-infrared fluorescence image-guided PDT.

Ultrasmall pH-responsive silicon phthalocyanine micelle for selective photodynamic therapy against tumor

Targeted photodynamic therapy (TPDT) based on the photosensitizers responsive for tumor microenvironment is promising because of the better anti-tumor effect and less phototoxicity against normal tissue than the traditional PDT. Nanoparticle-based stimuli-responsive photosensitizers have been widely explored for TPDT. Based on the acidic microenvironments in solid tumors, an ultrasmall pH-responsive silicon phthalocyanine nanomicelle (PSN) (smaller than 10[Formula: see text]nm) was designed for selective PDT of tumor. PSN had high drug loading efficacy (more than 28%) and exhibited morphological transitions, enhanced fluorescence and improved singlet oxygen yield under acidic environments. PSN was renal clearable and could rapidly accumulate and be retained at tumor sites, achieving a tumor-inhibiting effect better than phthalocyanine micelle without pH response. Tumors of mice treated with PSN for PDT were completely ablated without recurrence. Thus, we have developed a phthalocyanine-based pH-responsive micelle with excellent tumor targeting ability, which is expected to realize the selective PDT of tumor.

Identification and validation of four photodynamic therapy related genes inhibiting MAPK and inducing cell cycle alteration in squamous cell carcinoma.

IntroductionCutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer, and photodynamic therapy (PDT) is a promising modality against cSCC. This study investigated the impact of PDT on the MAPK pathway and cell cycle alternation of cSCC as well as the related molecular mechanisms.MethodExpressing mRNA profile data sets GSE98767, GSE45216, and GSE84758 were acquired from the GEO database. The functions of differently expressed genes (DEGs) were enriched by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Least absolute shrinkage and selection operator (Lasso) analysis were used to establish a diagnosis model based on GSE98767. A correlation analysis and a protein–protein interaction (PPI) network were used to evaluate the relationship between cSCC-PDT-related genes and the MAPK pathway. Single-sample gene set enrichment analysis (ssGSEA) was performed on GSE98767 to estimate MAPK activation and cell cycle activity. Finally, the effect of MAPK activation on the cell cycle was explored in vitro.ResultFour cSCC-PDT-related genes, DUSP6, EFNB2, DNAJB1, and CCNL1, were identified as diagnostic markers of cSCC, which were upregulated in cSCC or LC50 PDT-protocol treatment and negatively correlated with the MAPK promoter. Despite having a smaller MAPK activation score, cSCC showed higher cell cycle activity. The PDT treatment suppressed the G1 to G2/M phase in JNK overexpressed A431 cells.ConclusionCCNL1, DNAJB1, DUSP6, and EFNB2 were identified as potential PDT target genes in cSCC treatment, whose potential therapeutic mechanism was inhibiting the MAPK pathway and inducing cell cycle alternation.

Cathepsin B-Cleavable Polymeric Photosensitizer Prodrug for Selective Photodynamic Therapy: In Vitro Studies.

Cathepsin B is a lysosomal cysteine protease that plays an important role in cancer, atherosclerosis, and other inflammatory diseases. The suppression of cathepsin B can inhibit tumor growth. The overexpression of cathepsin B can be used for the imaging and photodynamic therapy (PDT) of cancer. PDT targeting of cathepsin B may have a significant potential for selective destruction of cells with high cathepsin B activity. We synthesized a cathepsin B-cleavable polymeric photosensitizer prodrug (CTSB-PPP) that releases pheophorbide a (Pha), an efficient photosensitizer upon activation with cathepsin B. We determined the concentration dependant uptake in vitro, the safety, and subsequent PDT-induced toxicity of CTSB-PPP, and ROS production. CTSB-PPP was cleaved in bone marrow cells (BMCs), which express a high cathepsin B level. We showed that the intracellular fluorescence of Pha increased with increasing doses (3–48 µM) and exerted significant dark toxicity above 12 µM, as assessed by MTT assay. However, 6 µM showed no toxicity on cell viability and ex vivo vascular function. Time-dependent studies revealed that cellular accumulation of CTSB-PPP (6 µM) peaked at 60 min of treatment. PDT (light dose: 0–100 J/cm2, fluence rate: 100 mW/cm2) was applied after CTSB-PPP treatment (6 µM for 60 min) using a special frontal light diffuser coupled to a diode laser (671 nm). PDT resulted in a light dose-dependent reduction in the viability of BMCs and was associated with an increased intracellular ROS generation. Fluorescence and ROS generation was significantly reduced when the BMCs were pre-treated with E64-d, a cysteine protease inhibitor. In conclusion, we provide evidence that CTSB-PPP showed no dark toxicity at low concentrations. This probe could be utilized as a potential imaging agent to identify cells or tissues with cathepsin B activity. CTSB-PPP-based PDT results in effective cytotoxicity and thus, holds great promise as a therapeutic agent for achieving the selective destruction of cells with high cathepsin B activity.

Asymmetric, amphiphilic RGD conjugated phthalocyanine for targeted photodynamic therapy of triple negative breast cancer

Targeted photodynamic therapy (TPDT) is considered superior to conventional photodynamic therapy due to the enhanced uptake of photosensitizers by tumor cells. In this paper, an amphiphilic and asymmetric cyclo-Arg-Gly-Asp-d-Tyr-Lys(cRGDyK)-conjugated silicon phthalocyanine (RSP) was synthesized by covalently attaching the tripeptide Arg-Gly-Asp (RGD) to silicone phthalocyanine in the axial direction for TPDT of triple-negative breast cancer (TNBC). RSP was characterized by spectroscopy as a monomer in physiological buffer. Meanwhile, the modification of RSP with RGD led to a high accumulation of the photosensitizer in TNBC cells overexpressing ανβ3 integrin receptors which can bind RGD, greatly reducing the risk of phototoxicity. In vitro photodynamic experiments showed that the IC50 of RSP was 295.96 nM in the 4T1 cell line, which caused significant apoptosis of the tumor cells. The tumor inhibition rate of RSP on the orthotopic murine TNBC achieved 74%, while the untargeted photosensitizer exhibited no obvious tumor inhibition. Overall, such novel targeted silicon phthalocyanine has good potential for clinical translation due to its simple synthesis route, strong targeting, and high therapeutic efficacy for TPDT treatment of TNBC.

Hybrid Inorganic-Organic Core-Shell Nanodrug Systems in Targeted Photodynamic Therapy of Cancer.

Hybrid inorganic-organic core-shell nanoparticles (CSNPs) are an emerging paradigm of nanodrug carriers in the targeted photodynamic therapy (TPDT) of cancer. Typically, metallic cores and organic polymer shells are used due to their submicron sizes and high surface to volume ratio of the metallic nanoparticles (NPs), combined with enhances solubility, stability, and absorption sites of the organic polymer shell. As such, the high loading capacity of therapeutic agents such as cancer specific ligands and photosensitizer (PS) agents is achieved with desired colloidal stability, drug circulation, and subcellular localization of the PS agents at the cancer site. This review highlights the synthesis methods, characterization techniques, and applications of hybrid inorganic-organic CSNPs as loading platforms of therapeutic agents for use in TPDT. In addition, cell death pathways and the mechanisms of action that hybrid inorganic-organic core-shell nanodrug systems follow in TPDT are also reviewed. Nanodrug systems with cancer specific properties are able to localize within the solid tumor through the enhanced permeability effect (EPR) and bind with affinity to receptors on the cancer cell surfaces, thus improving the efficacy of short-lived cytotoxic singlet oxygen. This ability by nanodrug systems together with their mechanism of action during cell death forms the core basis of this review and will be discussed with an overview of successful strategies that have been reported in the literature.

Molecular engineering of covalent organic frameworks with elevated mitochondrial-targeting for cancer cell suppression

Covalent organic frameworks (COFs) have appeared as a variety of promising nanomaterials for photodynamic therapy (PDT) owing to their excellent biosafety and structural diversity. However, finite aqueous dispersibility, deficient subcellular targeting ability and undesirable PDT efficiency had seriously restricted their biomedical application. Herein, we prepared two solution-dispersible nanoparticle COFs via a mild solution-phase synthesis, denoted as EB-TFP and DPP-TFP, investigating the effect of COF’s surface charges on their subcellular targeting ability and PDT efficiency. With tuning the COF’s surface charges, the positive charged COFs (EB-TFP) possessed the elevated mitochondrial targeting ability, higher O2-. generation ability and fluorescence at 510 nm. Therefore, EB-TFP successfully employed as multifunctional PSs with excellent mitochondrial targeting ability for the imaging-guided type Ⅰ PDT. This work provides a “killing two birds with one stone” strategy to improve subcellular targeting and ROS generation ability for expanding the biomedical applications via tuning the COFs’ surface charges.

Synthesis and Photothermal Effects of Intracellular Aggregating Nanodrugs Targeting Nasopharyngeal Carcinoma.

Chemotherapy for the treatment of nasopharyngeal carcinoma (NPC) is usually associated with many side effects; therefore, its treatment options have not yet been completely resolved. Improving distribution to the targeted tumor region and enhancing the cellular uptake of drugs can efficiently alleviate the above adverse medical effects. Near-infrared (NIR) laser light-mediated photothermal therapy (PTT) and photodynamic therapy (PDT) are promising strategies for cancer treatment. In the present study, we developed an efficient multifunctional nanocluster with enhanced targeting and aggregation efficiency for PTT and PDT that is composed of a biocompatible folic acid (FA), indocyanine green (ICG) and 2-cyanobenzothiazole (CBT)-functionalized peptide labeled with an aldehyde sodium alginate-modified magnetic iron oxide nanoparticle (ASA-MNP)-based nanocarrier. FA can bind to folate receptors on cancer cell membranes to enhance nanocluster uptake. CBT-modified peptide can react with glutathione (GSH), which is typically present at higher levels in cancer cells, to form intracellular aggregates and increase the local concentration of the nanodrug. In in vitro studies, these nanodrugs displayed the desired uptake capacity by NPC cells and the ability to suppress the growth of cancer cells under laser irradiation. Animal studies validated that these nanodrugs are safe and nontoxic, efficiently accumulate in NPC tumor sites following injection via the caudal vein, and shows superior inhibition of tumor growth in a tumor-bearing mouse model upon near-infrared laser irradiation. The results indicate the potential application of the multifunctional nanoparticles (NPs), which can be used as a new method for the treatment of folate receptor-positive NPC.

Quantum dots and photodynamic therapy in COVID ‐19 treatment

Viral diseases are regarded as a global burden. The eradication of viral diseases is always a challenging task in medical research due to the high infectivity and mutation capability of the virus. The ongoing COVID‐19 pandemic is still not under control even after several months of the first reported case and global spread. In the pursuit of a promising strategy, carbon dots could be considered as potential nanostructure against this viral pandemic. Carbon dots are photoluminescent carbon nanoparticles, smaller than 10 nm in dimension with a very attractive photostable and biocompatible properties which can be surfaced modified or functionalized. These photoluminescent tiny particles have captured much attention owing to their functionalization property and biocompatibility. Photodynamic therapy (PDT) is a technique that is widely used in cancer treatment and against various microbes. In this technique, a light‐induced photosensitizer generates reactive oxygen species (ROS), ultimately killing the target cells. Considering these facts, an attempt has been made to review the current literature on viral inactivation using PDT approach. Accordingly, the mechanism of PDT action has been discussed, along with an update on the use of various photosensitizers (PSs) and nanoparticles. The capsid proteins and nucleic acid (RNA) of SARS‐CoV‐2 can be a possible target for PDT.

Targeted Photodynamic Therapy Using Alloyed Nanoparticle-Conjugated 5-Aminolevulinic Acid for Breast Cancer.

Photodynamic therapy (PDT) has been investigated as an effective, non-invasive, and alternative tumor-ablative therapy that uses photosensitizers (PSs) and safe irradiation light in the presence of oxygen to generate reactive oxygen species (ROS) to kill malignant cancer cells. However, the off-target activation of the PSs can hinder effective PDT. Therefore, an advanced drug delivery system is required to selectively deliver the PS to the therapeutic region only and reduce off-target side effects in cancer treatment. The integration of laser-initiated PDT with nanotechnology has provided new opportunities in cancer therapy. In this study, plasmonic bimetallic nanoparticles (NPs) were prepared for the targeted PDT (TPDT) of in vitro cultured MCF-7 breast cancer cells. The NPs were functionalized with PEG through Au–thiol linkage to enhance their biocompatibility and subsequently attached to the PS precursor 5-aminolevulinic acid via electrostatic interactions. In order to enhance specific targeting, anti-HER-2 antibodies (Ab) were decorated onto the surface of the nanoconjugate (NC) to fabricate a 5-ALA/Au–Ag-PEG-Ab NC. In vitro studies showed that the synthesized NC can enter MCF-7 cells and localize in the cytoplasm to metabolize 5-ALA to protoporphyrin IX (PpIX). Upon light irradiation, PpIX can efficiently produce ROS for the PDT treatment of MCF-7. Cellular viability studies showed a decrease from 49.8% ± 5.6 ** to 13.8% ± 2.0 *** for free 5-ALA versus the NC, respectively, under equivalent concentrations of the PS (0.5 mM, IC50). These results suggest that the active targeted NC platform has an improved PDT effect on MCF-7 breast cancer cells.

Enhancing the tumor cell selectivity of a rhodamine-decorated iridium(III) complex by conjugating with indomethacin for COX-2 targeted photodynamic therapy

A rhodamine-iridium (III) complex bearing indomethacin moiety, named IM-rho-Ir, was synthesized and evaluated for COX-2 targetable photodynamic therapy. By integrating COX-2 directing group, IM-rho-Ir exhibited enhanced cellular uptake in cancer cells than in normal cells compared to rhodamine-iridium (III) complex without indomethacin moiety.

Good Steel Used in the Blade: Well‐Tailored Type‐I Photosensitizers with Aggregation‐Induced Emission Characteristics for Precise Nuclear Targeting Photodynamic Therapy

Photodynamic therapy (PDT) has long been recognized to be a promising approach for cancer treatment. However, the high oxygen dependency of conventional PDT dramatically impairs its overall therapeutic efficacy, especially in hypoxic solid tumors. Exploration of distinctive PDT strategy involving both high‐performance less‐oxygen‐dependent photosensitizers (PSs) and prominent drug delivery system is an appealing yet significantly challenging task. Herein, a precise nuclear targeting PDT protocol based on type‐I PSs with aggregation‐induced emission (AIE) characteristics is fabricated for the first time. Of the two synthesized AIE PSs, TTFMN is demonstrated to exhibit superior AIE property and stronger type‐I reactive oxygen species (ROS) generation efficiency owing to the introduction of tetraphenylethylene and smaller singlet–triplet energy gap, respectively. With the aid of a lysosomal acid‐activated TAT‐peptide‐modified amphiphilic polymer poly(lactic acid)12k–poly(ethylene glycol)5k–succinic anhydride‐modified TAT, the corresponding TTFMN‐loaded nanoparticles accompanied with acid‐triggered nuclear targeting peculiarity can quickly accumulate in the tumor site, effectively generate type‐I ROS in the nuclear region and significantly suppress the tumor growth under white light irradiation with minimized systematic toxicity. This delicate “Good Steel Used in the Blade” tactic significantly maximizes the PDT efficacy and offers a conceptual while practical paradigm for optimized cancer treatment in further translational medicine.

Apoptotic cell death induced by dendritic derivatives of aminolevulinic acid in endothelial and foam cells co-cultures.

Photodynamic therapy (PDT) is an effective procedure for the treatment of lesions diseases based on the selectivity of a photosensitising compound with the ability to accumulate in the target cell. Atherosclerotic plaque is a suitable target for PDT because of the preferential accumulation of photosensitisers in atherosclerotic plaques. Dendrimers are hyperbranched polymers conjugated to drugs. The dendrimers of ALA hold ester bonds that inside the cells are cleaved and release ALA, yielding PpIX production. The dendrimer 6m-ALA was chosen to perform this study since in previous studies it induced the highest porphyrin macrophage: endothelial cell ratio (Rodriguez et al. in Photochem Photobiol Sci 14:1617-1627, 2015). We transformed Raw 264.7 macrophages to foam cells by exposure to oxidised LDLs, and we employed a co-culture model of HMEC-1 endothelial cells and foam cells to study the affinity of ALA dendrimers for the foam cells. In this work it was proposed an in vitro model of atheromatous plaque, the aim was to study the selectivity of an ALA dendrimer for the foam cells as compared to the endothelial cells in a co-culture system and the type of cell death triggered by the photodynamic treatment. The ALA dendrimer 6m-ALA showed selectivity PDT response for foam cells against endothelial cells. A light dose of 1J/cm2 eliminate foam cells, whereas less than 50% of HMEC-1 is killed, and apoptosis cell death is involved in this process, and no necrosis is present. We propose the use of ALA dendrimers as pro-photosensitisers to be employed in photoangioplasty to aid in the treatment of obstructive cardiovascular diseases, and these molecules can also be employed as a theranostic agent.

Photodynamic Therapy (PDT): An Alternative Approach for Combating COVID-19

The COVID-19 disease initially originated in Wuhan (China) and then spread worldwide has been declared a pandemic by the World Health Organization (WHO). Many attempts are ongoing to find an effective therapeutic treatment and vaccine to cure or prevent the disease, but the success is very little. Even some of the approved vaccines are also disputed for safety issues. This is the time where we should think of alternative treatments to control the disease effectively. Photodynamic therapy (PDT) is a technique that is widely used in cancer treatment and against various microbes. In this technique, a light-induced photosensitizer generates reactive oxygen species (ROS), ultimately killing the target cells. Considering these facts, an attempt has been made to review the current literature on viral inactivation using PDT approach. Accordingly, the mechanism of PDT action has been discussed, along with an update on the use of various photosensitizers (PSs) and nanoparticles. The capsid proteins and nucleic acid (RNA) of SARS-CoV-2 can be a possible target for PDT. To understand this interaction further, computational modeling studies have been discussed to help design effective PSs. Overall, the PDT technique has therapeutic potential and should be tested as a complementary or alternative treatment for control of COVID-19 using the PSs like curcumin, psoralen derivatives, riboflavin, etc. This review discusses COVID-19, its outbreak, diagnosis, the existing treatment modalities, and how PDT can be an effective alternative treatment for controlling the disease.

Photodynamic therapy: apoptosis, paraptosis and beyond.

Photodynamic therapy (PDT) is a light-catalyzed process that can initiate cellular death pathways from the formation of cytotoxic reactive oxygen species at sub-cellular sites. Apoptosis was the first such pathway to be identified. Autophagy can also occur and is often found to be cytoprotective. Another process termed paraptosis can also have lethal consequences, even in cells with an impaired apoptotic pathway. PDT in vivo can evoke other potentially cytotoxic processes including vascular shutdown and enhanced immunologic recognition of neoplastic cells. Using appropriate photosensitizing agents, sub-cellular PDT targeting can be directed so that the resulting interplay among assorted death and survival pathways will result in an enhanced level of photokilling.