Photodynamic therapy (PDT) has gained considerable attention in cancer treatment due to its non-invasive nature and the ability of photosensitizers to generate reactive oxygen species upon light activation, leading to tumor destruction. Glutathione S-transferase P1 (GSTP1) is a key enzyme in chemotherapy resistance, often overexpressed in various cancers, and its inhibition of GSTP1 presents a promising strategy to enhance cancer treatment. This study is aimed at assessing the potential of prominent photosensitizers as GSTP1 inhibitors through molecular docking analysis to strengthen the efficacy of PDT. The photosensitizers were docked into the active site of GSTP1, and their binding affinities, inhibition constants (Ki), and molecular interactions were assessed. Among the tested photosensitizers, zinc phthalocyanine, hypericin, and temoporfin emerged as the top candidates, exhibiting binding energies of - 10.8, - 10.2, and - 9.8 kcal/mol, along with Ki values of 0.012, 0.033, and 0.064 µM, respectively. These compounds outperformed the reference inhibitor ethacrynic acid, which had a binding energy of - 6.6 kcal/mol and a Ki of 14.35 µM. These findings suggest that the dual action of these photosensitizers provides a promising strategy for combating cancer and overcoming treatment resistance.

A novel pheophorbide derivative, trimethyl-152-[L-aspartyl]pheophorbide a was synthesised and investigated for anti-tumor activity. The prepared photosensitizer had good absorption in the phototherapeutic window and high ROS yields. It exhibited excellent phototoxicity higher than reference compound m-THPC when irradiated by 650 nm light in vitro, and obvious photodynamic anti-tumor effect in vivo. It causes cellular apoptosis or necrosis under laser irradiation and localizes in mitochondria, lysosome, and endoplasmic reticulum. The observed high efficacy was rationalized by efficient introduction into the blood by facile transfer through membranes, which is supported by molecular dynamics simulation studies. This work provides a new candidate photosensitizer for anti-cancer treatment.

The escalating threat of antifungal resistance stemming from Trichosporon asahii (T. asahii) biofilms necessitates the pursuit of innovative therapeutic strategies. Among these approaches, 5-aminolevulinic acid (ALA) photodynamic therapy (PDT), an emerging therapeutic modality, has exhibited promising potential in eradicating T. asahii biofilms.

The inhibitory activity was evaluated by confocal laser scanning microscopy. To delve deeper into the efficacy of ALA-PDT in eliminating T. asahii biofilms, we conducted a comprehensive transcriptional analysis utilizing transcriptome sequencing.

ALA-PDT demonstrated a profound inhibitory effect on the viability of T. asahii biofilms. Our investigation unveiled 2720 differentially expressed genes following exposure to ALA-PDT. Subsequent meticulous scrutiny allowed for the annotation of genes with a ≥ twofold change in transcription, focusing on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. Particularly noteworthy were the upregulated genes associated with oxidation-reduction processes, oxidoreductase activity, and catalytic activity. Conversely, the downregulated genes were linked to ATP binding, protein phosphorylation, and protein kinase activity. Additionally, we observed a surge in the transcription of genes that may be involved in oxidative stress (e.g., A1Q1_05494) as well as genes that may be involved in morphogenesis and biofilm formation (e.g., A1Q1_04029, A1Q1_01345, A1Q1_08069, and A1Q1_01456) following ALA-PDT treatment.

Our findings underscore the substantial impact of ALA-PDT on the transcriptional regulation of genes related to oxidative stress, morphogenesis, and biofilm formation, paving the way for novel therapeutic avenues in combating T. asahii biofilms.

Verrucae (warts) are caused by human papilloma viruses. Photodynamic therapy (PDT) is a widely recommended option to treat warts.

To assess the role of liquid crystal loaded methylene blue (MB) combined with intense pulsed light (IPL) in the treatment of verrucae.

A total of 42 clinically and dermoscopically confirmed patients complaining of at least four cutaneous warts of various types were recruited in this clinical study. The lesions for the same patient were divided into 4 groups: Group (1) received topical 10% liquid crystal loaded MB, then was subjected to two passes of IPL with a 650 nm cutoff filter; Group (2) was subjected to two passes of IPL; and Group (3) received topical 10% liquid crystal loaded MB gel. They underwent four sessions at 2-week intervals. Group (4) was left with no treatment (control).

Complete disappearance of warts was observed in 52.4%, 19%, and 4.8% in Group 1, 2, and 3, respectively, with no recurrence throughout the following 3 months. Regarding PDT-treated group, verruca plantaris showed the best result, followed by verruca plana, then verruca vulgaris. Comparing all groups, there was a statistically significant difference in which the PDT group showed the best result.

PDT using 10% liquid crystal loaded MB combined with IPL is an effective option in wart treatment with the best results in V. plantaris, followed by V. plana and V. vulgaris.

Metronomic photodynamic therapy (mPDT) is a novel cancer treatment strategy that uses low-dose light delivery and photosensitizers. 5-aminolevulinic acid (5-ALA), a precursor of protoporphyrin IX (PpIX) was previously used to treat human colorectal and esophageal cancer cells. However, no study has evaluated the efficacy of 5-ALA-mPDT using light of different wavelengths. Therefore, we evaluated cytotoxicity induced by 5-ALA-PDT and the antitumor effect of 5-ALA-mPDT.

In an in vitro experiment, we evaluated the cytotoxicity induced by 5-ALA-PDT using several fluence rates of light-emitting diode (LED) at wavelengths of 532 and 620 nm. In an in vivo experiment, we evaluated the antitumor effect of 5-ALA-mPDT using a newly developed implantable device emitting 532 or 620 nm. Moreover, we used in silico simulations to compare the differences in the distribution of the accumulated singlet oxygen concentrations between 532 and 620 nm.

In the in vitro experiment, the percentages of late apoptotic/Dead and Dead cells in the 542-nm groups irradiated at light intensities of 1 mW/cm2 were significantly higher than those of cells in the 620-nm group. In contrast, in the in vivo experiment, the antitumor effect of mPDT using an implantable organic light-emitting diode (OLED) at 620 nm was significantly higher than that of mPDT using OLED at 542 nm.

Considering the results of our in silico study, the antitumor effect of 5-ALA-mPDT may be dependent on the distribution range of the accumulated singlet oxygen concentration rather than the accumulated singlet oxygen concentration.

In recent years, sonodynamic therapy (SDT) has attracted attention as a promising new approach for the treatment of high-grade gliomas, as it is a non-invasive form of therapy that specifically kills tumor cells with limited side effects. SDT combines low-intensity ultrasound with a sonosensitizer to produce cytotoxic effects in tumor cells. 5-Aminolevulinic acid (5-ALA), an endogenous amino acid that is metabolized to protoporphyrin IX (PpIX), has shown promise as a sonosensitizer for malignant gliomas in SDT. Ultrasound can penetrate deeper body regions and activate PpIX, leading to an increase in tumor immunogenicity and induction of apoptosis. This review highlights the current state of knowledge on the mechanisms of action, the results of preclinical, clinical and ongoing studies on 5-ALA-SDT in malignant gliomas, and discusses the future benefits of SDT.

Programmed cell death (PCD) plays a crucial role in oral cancer pathogenesis and treatment. However, a comprehensive bibliometric analysis of the global research landscape in this field has not been conducted. This study aims to analyze the evolution and current trends of PCD research in oral cancer from 2000 to 2024.

Publications were retrieved from the Web of Science Core Collection database using relevant keywords related to oral cancer and PCD. VOSviewer 1.6.20 and CiteSpace 6.1R6 software were employed to conduct bibliometric analysis, including publication trends, citation analysis, co-authorship networks, keyword co-occurrence, and research hotspots. The time span was set from January 2000 to December 2024.

A total of 963 publications were identified and analyzed. The annual publication output showed a steady increase, with a significant growth rate after 2010, dividing the study period into three distinct phases. The most productive countries were China (58.42%), South Korea (12.27%), and Japan (10.04%), with China Medical University and Kaohsiung Medical University being the leading institutions. Research hotspots evolved from traditional apoptosis studies to emerging forms of PCD such as autophagy, ferroptosis, and pyroptosis. Keyword analysis revealed three major research clusters: basic molecular mechanisms (centered around ROS and oxidative stress), clinical aspects (including prognosis and cell proliferation), and cell death pathways. Citation burst analysis identified emerging trends in targeting multiple PCD pathways simultaneously for oral cancer therapy, with special focus on treatment resistance and survival.

This bibliometric analysis provides a comprehensive overview of global research trends in PCD and oral cancer over the past two decades. The findings highlight the shift from basic mechanistic studies focusing on apoptosis to more diverse PCD pathways and translational research. Emerging research directions include the exploration of synergistic mechanisms among multiple PCD pathways, development of AI-based personalized treatment plans, investigation of microenvironment regulation of PCD, and application of novel drug delivery systems. These trends demonstrate the field's evolution toward more integrated, personalized approaches in oral cancer treatment. This study offers valuable insights for researchers and funding agencies to identify research gaps and potential collaboration opportunities in this rapidly developing field.

Cancer is one of the main causes of death worldwide. Chemotherapy, radiotherapy and surgery are currently the treatments of choice for cancer. However, conventional therapies have their limitations, such as non-specificity, tumor recurrence and toxicity to the target cells. Recently, nanomaterials have been considered as therapeutic agents against cancer. This is mainly due to their unique optical properties, biocompatibility, large surface area and nanoscale size. These properties are crucial as they can affect biocompatibility and uptake by the cell, reducing efficacy. However, because nanoparticles can be functionalized with biomolecules, they become more biocompatible, which improves uptake, and they can be specifically targeted against cancer cells, which improves their anticancer activity. In this review, we summarize some of the recent studies in which nanomaterials have been functionalized with the aim of increasing therapeutic efficacy in cancer treatment.

Introduction: Oral infections pose significant public health challenges, often exacerbating other comorbidities and increasing systemic health risks. Traditional treatments often fail to eliminate persistent micro-organisms and contribute to the rise of antimicrobial resistance. Nanoparticulate systems offer a promising solution by delivering active agents directly to targeted sites, providing more effective and localized treatment options. Objective: This study aimed to synthesize and characterize methylcellulose nanoparticles containing methylene blue at different concentrations using the nanoprecipitation method. We also evaluated their biocompatibility and antimicrobial activity against key micro-organisms commonly found in oral infections. Methods: The study involved physicochemical and morphological characterizations, including encapsulation efficiency, particle size, polydispersity index, zeta potential, and transmission electron microscopy (TEM). Additionally, controlled release profiles, antimicrobial efficacy against major oral pathogens, and biocompatibility in vitro assessments were performed. Results: The results revealed encapsulation efficiency between 99.1 and 98.8%, with particle sizes ranging from 186 to 274 nm and a zeta potential of 1.7 to 2.9 mV achieved at lower concentrations of methylene blue and methylcellulose. The nanoparticles demonstrated sustained drug release of 85% for the smaller particles and 45% for the larger particles for more than 10 h. The nanoparticles exhibited superior antimicrobial activity compared to pure methylene blue. Cell viability studies indicated that the nanoparticles were biocompatible with approximately 40% cell viability at lower concentrations of the nanoparticles. Conclusions: These findings suggest that methylene blue nanoparticles could serve as a promising adjunct in dental treatments. They offer targeted antimicrobial action while potentially reducing the development of antimicrobial resistance.

The abscopal effect is a phenomenon wherein localised therapy on the primary tumour leads to regression of distal metastatic growths. Interestingly, various pre-clinical studies utilising sonodynamic therapy (SDT) have reported significant abscopal effects, however, the mechanism remains largely enigmatic. SDT is an emerging non-invasive cancer treatment that uses focussed ultrasound (FUS) and a sonosensitiser to induce tumour cell death. To expand our understanding of abscopal effects of SDT, we have summarised the preclinical studies that have found SDT-induced abscopal responses across various cancer models, using diverse combination strategies with nanomaterials, microbubbles, chemotherapy, and immune checkpoint inhibitors. Additionally, we shed light on the molecular and immunological mechanisms underpinning SDT-induced primary and metastatic tumour cell death, as well as the role and efficacy of different sonosensitisers. Notably, the observed abscopal effects underscore the need for continued investigation into the SDT-induced 'vaccine-effect' as a potential strategy for enhancing systemic anti-tumour immunity and combating metastatic disease. The results of the first SDT human clinical trials are much awaited and are hoped to enable the further evaluation of the safety and efficacy of SDT, paving the way for future studies specifically designed to explore the potential of translating SDT-induced abscopal effects into clinical reality.

Photoagents with ultra-high near-infrared II (NIR-II) light energy conversion efficiency hold great promise in tumor phototherapy due to their ability to penetrate deeper tissues and minimize damage to surrounding healthy cells. However, the development of NIR-II photoagents remain challenging. In this study, an all-fused-ring quinoidal acceptor-donor-acceptor (A-D-A) molecule, SKCN, with a BTP core is synthesized, and nanoparticles named FA-SNPs are prepared. The unique quinoidal structure enhances π-electron delocalization and bond length uniformity, significantly reducing the bandgap of SKCN, resulting in strong NIR-II absorption, a high molar extinction coefficient, and a photothermal conversion efficiency of 75.14%. Enhanced molecular rigidity also facilitates efficient energy transfer to oxygen, boosting reactive oxygen species generation. By incorporating the immunomodulator R848, FA-SRNPs nanoparticles are further developed, effectively modulating the tumor immune microenvironment by reducing Tregs and M-MDSCs infiltration, promoting dendritic cell maturation, M1 macrophage polarization, and activating CD8+ T cells and NK cells. Comprehensive studies using orthotopic ovarian cancer models demonstrated strong tumor targeting, photoacoustic imaging capabilities, and significant tumor suppression and metastasis inhibition, and also showing excellent therapeutic efficacy in an orthotopic breast cancer model. This study provides strong evidence for the potential application of quinoidal A-D-A molecules in cancer photoimmunotherapy.

Novel pH-sensitive polymeric photosensitizer carriers from the phthalocyanine (Pc) group were investigated as potential photodynamic therapy drugs for the treatment of breast cancer. Their high antiproliferative activity was confirmed by photocytotoxicity studies, which indicated their high efficacy and specificity toward the SK-BR-3 cell line. Importantly, the Pcs encapsulated in the polymeric nanoparticle (NP) carrier exhibited a much better penetration into the acidic environment of tumor cells than their free form. The investigated Pc4-NPs and TT1-NPs exhibited a high selectivity to healthy fibroblasts as well as non-toxicity without irradiation. This paper describes the detailed mechanism of action of the evaluated compounds by measuring reactive oxygen species (ROS), including singlet oxygen; imaging cellular localization; and analyzing key signaling pathway proteins. An additional advantage of the evaluated compounds is their ability to inhibit the Akt protein expression, including its phosphorylation, which the Western blot test confirmed. This is particularly important because breast cancers often overexpress the HER-2 receptor-related signaling proteins. Moreover, an analysis of proteins such as GLUT-1, HO-1, phospho-p42/44, and BID revealed the significant involvement of ROS in disrupting cellular homeostasis, thereby leading to the induction of oxidative stress and resulting in apoptotic cell death.

Hypericin (HP), a natural photosensitizer, has demonstrated great efficacy in photodynamic therapy (PDT) for cancer treatment. In addition to the induction of apoptosis and necrosis through reactive oxygen species (ROS) generation, the therapeutic mechanisms and targets of PDT-HP remain unknown.

To investigate the direct targets and mechanisms of action of photoactivated hypericin in the inhibition of triple-negative breast cancer (TNBC).

Cell pyroptosis was examined via LDH release, SYTOX Green staining, and ELISA. RNA sequencing, network pharmacology, drug affinity target stability (DARTS)-tandem mass spectrometry (MS/MS), and molecular docking were employed to identify drug targets. Furthermore, immunoblotting and flow cytometry were utilized to elucidate the mechanisms of drug action.

Our research revealed that PDT-HP can induce pyroptosis in TNBC cells. Further investigation revealed that PDT-HP induces endoplasmic reticulum stress, activating Caspase-3 and gasdermin E (GSDME) to trigger TNBC cell pyroptosis. RNA-seq, network pharmacology, and DARTS-MS/MS proteomic analyses revealed that the endoplasmic reticulum protein calreticulin (CALR) is a potential HP target and that interfering with CALR inhibited PDT-HP-induced pyroptosis. During PDT-HP treatment, the interaction between CALR and SERCA2 inactivates SERCA2, increasing the susceptibility of cells to increased intracellular Ca2+ levels under oxidative stress. This triggered endoplasmic reticulum stress and activated Caspase3, which further cleaved GSDME, releasing GSDME-N and ultimately leading to pyroptosis in TNBC cells.

In this study, we provide insight into the antitumor mechanism by examining the pharmacological mechanism by which PDT-HP regulates TNBC cell pyroptosis via the ROS/CALR/Caspase-3/GSDME signaling axis.

Photodynamic therapy is a non-ionizing radiation treatment that utilizes a photosensitizer in combination with light to produce singlet oxygen. This singlet oxygen induces anti-cancer effects by causing apoptotic, necrotic, or autophagic cell death in tumor cells. Currently, photodynamic therapy is employed in oncology to treat various cancers. In the presence of oxygen, this non-invasive approach leads to direct tumor cell death, damage to microvasculature, and the induction of a local inflammatory response. These effects allow photodynamic therapy to be effective in treating early-stage tumors, extending survival in cases where surgery is not feasible, and significantly improving quality of life. In this paper, we provide a state of the art on cytomolecular mechanisms and associated pathways involved in photodynamic therapy. By integrating these mechanistic insights with the most recent advancements in nanotechnology, this phototherapeutic approach has the potential to become a prevalent treatment option within conventional cancer therapies, enhancing its application in precision medicine.

Photodynamic Therapy (PDT) is a therapeutic modality that combines the application of a photoactive compound (photosensitizer, PS) with low-power light to generate reactive oxygen species in the target tissue, resulting in cytotoxic damage and cell death, while sparing adjacent tissues. The objective of this study was to evaluate the phototoxicity of a cyanine dye with two chromophores (biscyanines, BCD) in systems with varying levels of cellular organization, and we used the Photogem® (a photosensitizer approved by the Brazilian ANVISA agency for clinical use in Photodynamic Therapy) as a positive control.

The cytotoxicity of the compounds was assessed in vitro in 2D monolayers, 3D spheroid cultures, and artificial skin models. Four tumoral cell lines A375 (melanoma), HCB-541 (cutaneous squamous cell carcinoma), Vu120T and Vu147T (head and neck cancer), and two normal cell lines fibroblastic HFF-1 and keratinocyte HACAT were used in this study. Cell viability, migration, production of reactive oxygen species, expression of proteins linked to DNA damage and repair, internalization, and skin permeation of PS agents.

Light irradiation in the presence of the PS resulted in greater cytotoxic effects for BCD as compared to Photogem®, which was accompanied by an increase in the production of reactive oxygen species including H2O2, elevated levels of cleaved PARP, and a higher rate of phosphorylated H2AX protein. BCD demonstrated enhanced internalization and bioaccumulation in the spheroids and equivalent skin models.

BCD, as a photosensitizer, showed higher cytotoxicity, with an increased ability to generate reactive oxygen species. This led to reduced cell viability, inhibited migration, and upregulated DNA damage-related proteins. Additionally, its enhanced cellular uptake improved skin barrier permeability, making BCD a strong candidate for in vivo Photodynamic Therapy.

Photodynamic therapy is a curative treatment of human papillomavirus-associated diseases that provides a selective effect leading to the destruction of pathological cells containing the virus. The retrospective study aimed to determine the role of systemic inflammatory reaction induced by photodynamic stimulation in low- and high-squamous intraepithelial lesion treatment.

143 patients with confirmed human papillomavirus-associated cervical intraepithelial neoplasia underwent photodynamic therapy with Photolon and activation in the range of 662 nm. All patients underwent colposcopy, histologic study, HPV DNA analysis, CBC, and immunogram. The chi-square criterion was used to evaluate differences before, 5 days post, and 3 months after PDT; a P value <0.05 was considered significant.

A complete regression in patients with low-squamous intraepithelial lesion (n=117) was achieved 3 months after PDT in 89.7% of cases (105/117) while it persisted in 12 patients. Complete regression in patients with high-squamous intraepithelial lesion (n=26) was achieved in 92.3% (24/26), one patient retained with the lesion, and another one had partial regression in the form of lower grade lesion. On the 5th day post-PDT, the formation of dense fibrin in photodynamic effect was noted on colposcopy, and changes in CBC, accompanied by statistically significant neutrocytosis, increased ESR and other indicators of reactive inflammation were recorded. Patients noted increased body temperature up to 37.8±0.5°C in 88% of cases.

One of the mechanisms of PDT`s antitumor and antiviral action is the development of acute inflammation in response to cytotoxic action on cells and vascular response in the form of pathological area devascularization. Such reactive inflammation activates all parts of the immune system. Changes on day 5 post-PDT in inflammatory parameters in CBC and IL-1, IL-6 and TNF-α markers correlate with the clinical picture of the post-photodynamic effect.

Cancer is a global concern worldwide. Prostate cancer has high prevalence and mortality rates among men. Photodynamic therapy (PDT) is an alternative treatment that is promising and effective with fewer side-effects than conventional therapies. However, some factors may limit its efficacy. For this, PDT can be combined with other modalities such as photobiomodulation (PBM) which is commonly used for increased cell proliferation/differentiation and wound healing. In this study, PBM pre-treatment at 655 nm of wavelength with 1, 3, and 5 J/cm2 energy densities was applied to prostate cancer cells to investigate its role in indocyanine green (ICG)-mediated PDT applications. Following PBM treatment, various analyses were assessed including cell viability, cellular uptake of ICG, ATP production, nitric oxide release, reactive oxygen species generation, and the changes in mitochondrial membrane potential. Increased cell death was observed with the PBM pre-treatment at 1 and 3 J/cm2 energy densities depending on ICG incubation time. Intracellular ROS generation and nitric oxide release by PBM had a significant impact on anticancer PDT action. An enhanced anticancer PDT effect was obtained with the PBM pre-treatment which may become a valuable modality to increase the sensitivity of the cancerous cells to PDT applications.

Oral squamous cell carcinoma (OSCC) is a common malignancy in the oral cavity. Photodynamic therapy (PDT) is a new alternative for the treatment of diseases using photosensitizers (PS) and light. In this study, we used a photosensitizer complex (Ce6-MnNPs-Chlorin e6 combined with up-conversion nanoparticles NaYF4:Yb/Er/Mn) to investigate the therapeutic effectiveness of this treatment against oral cancer cells. We also investigated the mechanism of action of near-infrared light PDT (NIR-PDT) combined with the Ce6-MnNPs. After determining a suitable concentration of Ce6-MnNPs using an MTT assay, human oral squamous cell carcinoma cells (HSC-3) were treated with NIR-PDT with Ce6-MnNPs. We examined the characteristics of Ce6-MnNPs by transmission electron microscopy (TEM); a zeta potential and particle size analyzer; Fourier-transform infrared spectroscopy (FTIR); cell viability by MTT assay; and apoptosis by FITC-Annexin V/PI assay. The mitochondrial membrane potential (MMP), apoptosis-related mRNA level (Bax and Bcl-2) and p53 protein were also researched. NIR-PDT with 0.5 ng/µL Ce6-MnNPs inhibited the proliferation of HSC-3 (p < 0.05). After treatment with NIR-PDT, changes in the mitochondrial membrane potential and apoptosis occurred (p < 0.01). The ratio of Bax/Bcl-2 and p53-positive cells increased (p < 0.01). These results suggest that this treatment can induce apoptosis of oral cancer cells.

Photodynamic therapy (PDT) employing two-photon (TP) excitation is increasingly recognized to induce cell damage selectively in targeted areas, underscoring the importance of developing TP photosensitizers (TP-PSs). In this study, we developed BSe-B, a novel PS that combines a selenium containing dye with biotin, a cancer-selective ligand, and is optimized for TP excitation. BSe-B demonstrated enhanced cancer selectivity, efficient generation of type-I based reactive oxygen species (ROS), low dark toxicity, and excellent cell-staining capability. Evaluation across diverse cell lines (HeLa, A549, OVCAR-3, WI-38, and L-929) demonstrated that BSe-B differentiated and targeted cancer cells while sparing normal cells. BSe-B displayed excellent in vivo biocompatibility. In cancer models such as three-dimensional spheroids and actual colon cancer tissues, BSe-B selectively induced ROS production and cell death under TP irradiation, demonstrating precise spatial control. These findings highlight the potential of BSe-B for imaging-guided PDT and its capability for micro treatment within tissues. Thus, BSe-B demonstrates robust TP-PDT capabilities, making it a promising dual-purpose tool for cancer diagnosis and treatment.

Photodynamic therapy (PDT) represents a targeted approach for cancer treatment that employs light and photosensitizers (PSs) to induce the generation of reactive oxygen species (ROS). However, PDT faces obstacles including insufficient PS localization, limited light penetration, and treatment resistance. A potential solution lies in nanogenerators (NGs), which function as self-powered systems capable of generating electrical energy. Recent progress in piezoelectric and triboelectric NGs showcases promising applications in cancer research and drug delivery. Integration of NGs with PDT holds the promise of enhancing treatment efficacy by ensuring sustained PS illumination, enabling direct electrical control of cancer cells, and facilitating improved drug administration. This comprehensive review aims to augment our comprehension of PDT principles, explore associated challenges, and underscore the transformative capacity of NGs in conjunction with PDT. By harnessing NG technology alongside PDT, significant advancement in cancer treatment can be realized. Herein, we present the principal findings and conclusions of this study, offering valuable insights into the integration of NGs to overcome barriers in PDT.

Among various cancer treatment methods, photodynamic therapy has received significant attention due to its non-invasiveness and high efficiency in inhibiting tumour growth. Recently, specific organelle targeting photosensitizers have received increasing interest due to their precise accumulation and ability to trigger organelle-mediated cell death signalling pathways, which greatly reduces the drug dosage, minimizes toxicity, avoids multidrug resistance, and prevents recurrence. In this review, recent advances and representative photosensitizers used in targeted photodynamic therapy on organelles, specifically including the endoplasmic reticulum, Golgi apparatus, mitochondria, nucleus, and lysosomes, have been comprehensively reviewed with a focus on organelle structure and organelle-mediated cell death signalling pathways. Furthermore, a perspective on future research and potential challenges in precision photodynamic therapy has been presented at the end.

Glioblastoma is a malignant neoplasm that develops in the central nervous system and is characterized by high rates of cell proliferation and invasion, presenting resistance to treatments and a poor prognosis. Photodynamic therapy (PDT) is a therapeutic modality that can be applied in oncological cases and stands out for being less invasive. Photosensitizers (PS) of natural origin gained prominence in PDT. Curcumin (CUR) is a natural compound that has been used in PDT, considered a promising PS. In this work, we evaluated the effects of PDT-mediated CUR and near-infrared radiation (NIR) in glioblastoma cells. Through trypan blue exclusion analysis, we chose the concentration of 5 μM of CUR and the dose of 2 J/cm2 of NIR that showed better responses in reducing the viable cell number in the C6 cell line and did not show cytotoxic/cytostatic effects in the HaCat cell line. Our results show that there is a positive interaction between CUR and NIR as a PDT model since there was an increase in ROS levels, a decrease in cell proliferation, increase in cytotoxicity with cell death by autophagy and necrosis, in addition to the presence of oxidative damage to proteins. These results suggest that the use of CUR and NIR is a promising strategy for the antitumor application of PDT.

Photodynamic therapy (PDT) is a clinically approved therapeutic modality for treating oncological and non-oncological disorders. PDT has proclaimed multiple benefits over further traditional cancer therapies including its minimal systemic toxicity and selective ability to eliminate irradiated tumors. In PDT, a photosensitizing substance localizes in tumor tissues and becomes active when exposed to a particular wavelength of laser light. This produces reactive oxygen species (ROS), which induce neoplastic cells to die and lead to the regression of tumors. The contributions of ROS to PDT-induced tumor destruction are described by three basic processes including direct or indirect cell death, vascular destruction, and immunogenic cell death. However, the efficiency of PDT is significantly limited by the inherent nature and tumor microenvironment. Combining immunotherapy with PDT has recently been shown to improve tumor immunogenicity while decreasing immunoregulatory repression, thereby gently modifying the anticancer immune response with long-term immunological memory effects. This review highlights the fundamental ideas, essential elements, and mechanisms of PDT as well as nanomaterial-based PDT to boost tumor immunogenicity. Moreover, the synergistic use of immunotherapy in combination with PDT to enhance immune responses against tumors is emphasized.

Cyclotriphosphazene (CP) is a cyclic inorganic compound with the chemical formula N3P3. This unique molecule consists of a six-membered ring composed of alternating nitrogen and phosphorus atoms, each bonded to two chlorine atoms. CP exhibits remarkable versatility and significance in the realm of materials chemistry due to its easy functionalization via facile nucleophilic substitution reactions in mild conditions as well as intriguing properties of resultant final CP-based molecules or polymers. CP has been served as an important building block for numerous functional materials. This review provides a general and broad overview of the synthesis of CP-based small molecules through nucleophilic substitution of hexachlorocyclotriphosphazene (HCCP), and their applications, including flame retardants, liquid crystals (LC), chemosensors, electronics, biomedical materials, and lubricants, have been summarized and discussed. It would be expected that this review would offer a timely summary of various CP-based materials and hence give an insight into further exploration of CP-based molecules in the future.

Compared with conventional therapies, photoimmunotherapy offers precise targeted cancer treatment with minimal damage to healthy tissues and reduced side effects, but its efficacy may be limited by shallow light penetration and the potential for tumor resistance. Here, an acceptor-donor-acceptor (A-D-A)-structured nanoaggregate is developed with dual phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), triggered by single near-infrared (NIR) light. Benefiting from strong intramolecular charge transfer (ICT), the A-D-A-structured nanoaggregates exhibit broad absorption extending to the NIR region and effectively suppressed fluorescence, which enables deep penetration and efficient photothermal conversion (η = 67.94%). A suitable HOMO-LUMO distribution facilitates sufficient intersystem crossing (ISC) to convert ground-state oxygen (3O2) to singlet oxygen (1O2) and superoxide anions (·O2 -), and catalyze hydroxyl radical (·OH) generation. The enhanced ICT and ISC effects endow the A-D-A structured nanoaggregates with efficient PTT and PDT for cervical cancer, inducing efficient immunogenic cell death. In combination with clinical aluminum adjuvant gel, a novel photoimmunotherapy strategy for cervical cancer is developed and demonstrated to significantly inhibit primary and metastatic tumors in orthotopic and intraperitoneal metastasis cervical cancer animal models. The noninvasive therapy strategy offers new insights for clinical early-stage and advanced cervical cancer treatment.

Oral cancers, specifically oral squamous cell carcinoma (OSCC), pose a significant global health challenge, with high incidence and mortality rates. Conventional treatments such as surgery, radiotherapy, and chemotherapy have limited effectiveness and can result in adverse reactions. However, as an alternative, photodynamic therapy (PDT) has emerged as a promising option for treating oral cancers. PDT involves using photosensitizing agents in conjunction with specific light to target and destroy cancer cells selectively. The photosensitizers accumulate in the cancer cells and generate reactive oxygen species (ROS) upon exposure to the activating light, leading to cellular damage and ultimately cell death. PDT offers several advantages, including its non-invasive nature, absence of known long-term side effects when administered correctly, and cost-effectiveness. It can be employed as a primary treatment for early-stage oral cancers or in combination with other therapies for more advanced cases. Nonetheless, it is important to note that PDT is most effective for superficial or localized cancers and may not be suitable for larger or deeply infiltrating tumors. Light sensitivity and temporary side effects may occur but can be managed with appropriate care. Ongoing research endeavors aim to expand the applications of PDT and develop novel photosensitizers to further enhance its efficacy in oral cancer treatment. This review aims to evaluate the effectiveness of PDT in treating oral cancers by analyzing a combination of preclinical and clinical studies.

As a precursor of protoporphyrin IX (PpIX), an endogenous pro-apoptotic and fluorescent molecule, 5-Aminolevulinic acid (5-ALA) has gained substantial attention for its potential in fluorescence-guided surgery as well as photodynamic therapy (PDT). Moreover, 5-ALA-PDT has been suggested as a promising chemo-radio sensitization therapy for various cancers. However, insufficient 5-ALA-induced PpIX fluorescence and the induction of multiple resistance mechanisms may hinder the 5-ALA-PDT clinical outcome. Reduced efficacy and resistance to 5-ALA-PDT can result from genomic alterations, tumor heterogeneity, hypoxia, activation of pathways related to cell surveillance, production of nitric oxide, and most importantly, deregulated 5-ALA transporter proteins and heme biosynthesis enzymes. Understanding the resistance regulatory mechanisms of 5-ALA-PDT may allow the development of effective personalized cancer therapy. Here, we described the mechanisms underlying resistance to 5-ALA-PTD across various tumor types and explored potential strategies to overcome this resistance. Furthermore, we discussed future approaches that may enhance the efficacy of treatments using 5-ALA-PDT.

Type I photodynamic therapy (PDT) generates reactive oxygen species (ROS) through oxygen-independent photoreactions, making it a promising method for treating hypoxic tumors. However, the superoxide anion (O2∙-) generated usually exhibits a low oxidation capacity, restricting the antitumor efficacy of PDT in clinical practice. Herein, a photoactivated self-assembled nanoreactor (1-NBS@CeO2) is designed through integration of type I PDT and cerium oxide (CeO2) nanozymes for inducing cascade-amplified oxidative stress in hypoxic tumors. The nanoreactor is constructed though co-assembly of an amphiphilic peptide (1-NBS) and CeO2, giving well-dispersed spherical nanoparticles with enhanced superoxide dismutase (SOD)-like and peroxidase (POD)-like activities. Following light irradiation, 1-NBS@CeO2 undergoes type I photoreactions to generated O2∙-, which is further catalyzed by the nanoreactors, ultimately forming hypertoxic hydroxyl radical (∙OH) through cascade-amplified reactions. The PDT treatment using 1-NBS@CeO2 results in elevation of intracellular ROS and depletion of GSH content in A375 cells, thereby inducing mitochondrial dysfunction and triggering apoptosis and ferroptosis of tumor cells. Importantly, intravenous administration of 1-NBS@CeO2 alongside light irradiation showcases enhances antitumor efficacy and satisfactory biocompatibility in vivo. Together, the self-assembled nanoreactor facilitates cascade-amplified photoreactions for achieving efficacious type I PDT, which holds great promise in developing therapeutic modules towards hypoxic tumors.

Medicinal plant-mediated combinational therapies have gained importance globally due to minimal side effects and enhanced treatment outcomes compared to single-drug modalities. We aimed to analyze the cytotoxic potential of each conventional treatment i.e., photodynamic therapy (PDT), chemotherapy (doxorubicin hydrochloride; Dox-HCl) with or without various concentrations of medicinal plant extracts (PE) on soft tissue cancer Rhabdomyosarcoma (RD) cell line.

The Rhabdomyosarcoma (RD) cell line was cultured and treated with Photosensitizer (Photosense (AlPc4)), Chemo (Dox-HCl), and their combinations with different concentrations of each plant extract i.e., Thuja occidentalis, Moringa oleifera, Solanum surattense. For the source of illumination, a Diode laser (λ = 630 nm ± 1 nm, Pmax = 1.5 mW) was used. Photosensitizer uptake time (∼ 45 min) was optimized through spectrophotometric measurements (absorption spectroscopy). Drug response of each treatment arm was assessed post 24 h of administration using 3-(4, 5-dimethyl-2-thiazolyl)-2, 5- 5-diphenyl-2 H- tetrazolium bromide (MTT) assay.

PE-mediated Chemo-Photodynamic therapy (PDT) exhibited synergistic effects (CI < 1). Moreover, Rhabdomyosarcoma culture pretreated with various plant extracts for 24 h exhibited significant inhibition of cell viability however most effective outcomes were shown by low and high doses of Moringa oleifera compared to other plant extracts. Post low doses treated culture with all plant extracts followed by PDT came up with more effectiveness when compared to all di-therapy treatments.

The general outcome of this work shows that the ethanolic plant extracts (higher doses) promote the death of cancerous cells in a dose-dependent way and combining Dox-HCl and photo-mediated photodynamic therapy can yield better therapeutic outcomes.

According to international cancer data, breast cancer (BC) is the leading type of cancer in women. Although significant progress has been made in treating BC, metastasis and drug resistance continue to be the primary causes of mortality for many patients. Reactive oxygen species (ROS) play a dual role in vivo: normal levels can maintain the body's normal physiological function; however, high levels of ROS below the toxicity threshold can lead to mtDNA damage, activation of proto-oncogenes, and inhibition of tumor suppressor genes, which are important causes of BC. Differences in the production and regulation of ROS in different BC subtypes have important implications for the development and treatment of BC. ROS can also serve as an important intracellular signal transduction factor by affecting the antioxidant system, activating MAPK and PI3K/AKT, and other signal pathways to regulate cell cycle and change the relationship between cells and the activity of metalloproteinases, which significantly impacts the metastasis of BC. Hypoxia in the BC microenvironment increases ROS production levels, thereby inducing the expression of hypoxia inducible factor-1α (HIF-1α) and forming "ROS- HIF-1α-ROS" cycle that exacerbates BC development. Many anti-BC therapies generate sufficient toxic ROS to promote cancer cell apoptosis, but because the basal level of ROS in BC cells exceeds that of normal cells, this leads to up-regulation of the antioxidant system, drug efflux, and apoptosis inhibition, rendering BC cells resistant to the drug. ROS crosstalks with tumor vessels and stromal cells in the microenvironment, increasing invasiveness and drug resistance in BC.

The cell membrane is a crucial component of cells, protecting their integrity and stability while facilitating signal transduction and information exchange. Therefore, disrupting its structure or impairing its functions can potentially cause irreversible cell damage. Presently, the tumor cell membrane is recognized as a promising therapeutic target for various treatment methods. Given the extensive research focused on cell membranes, it is both necessary and timely to discuss these developments, from materials design to specific biomedical applications. This review covers treatments based on functional materials targeting the cell membrane, ranging from well-known membrane-anchoring photodynamic therapy to recent lysosome-targeting chimaeras for protein degradation. The diverse therapeutic mechanisms are introduced in the following sections: membrane-anchoring phototherapy, self-assembly on the membrane, in situ biosynthesis on the membrane, and degradation of cell membrane proteins by chimeras. In each section, we outline the conceptual design or general structure derived from numerous studies, emphasizing representative examples to understand advancements and draw inspiration. Finally, we discuss some challenges and future directions in membrane-targeted therapy from our perspective. This review aims to engage multidisciplinary readers and encourage researchers in related fields to advance the fundamental theories and practical applications of membrane-targeting therapeutic agents.

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.

Photodynamic therapy (PDT) represents an emerging strategy to treat various malignancies, including colorectal cancer (CC), the third most common cancer type. This work presents an engineered M13 phage retargeted towards CC cells through pentavalent display of a disulfide-constrained peptide nonamer. The M13CC nanovector was conjugated with the photosensitizer Rose Bengal (RB), and the photodynamic anticancer effects of the resulting M13CC-RB bioconjugate were investigated on CC cells. We show that upon irradiation M13CC-RB is able to impair CC cell viability, and that this effect depends on i) photosensitizer concentration and ii) targeting efficiency towards CC cell lines, proving the specificity of the vector compared to unmodified M13 phage. We also demonstrate that M13CC-RB enhances generation and intracellular accumulation of reactive oxygen species (ROS) triggering CC cell death. To further investigate the anticancer potential of M13CC-RB, we performed PDT experiments on 3D CC spheroids, proving, for the first time, the ability of engineered M13 phage conjugates to deeply penetrate multicellular spheroids. Moreover, significant photodynamic effects, including spheroid disruption and cytotoxicity, were readily triggered at picomolar concentrations of the phage vector. Taken together, our results promote engineered M13 phages as promising nanovector platform for targeted photosensitization, paving the way to novel adjuvant approaches to fight CC malignancies.

Skin cancer (SC) poses a global threat to the healthcare system and is expected to increase significantly over the next two decades if not diagnosed at an early stage. Early diagnosis is crucial for successful treatment, as the disease becomes more challenging to cure as it progresses. However, identifying new drugs, achieving clinical success, and overcoming drug resistance remain significant challenges. To overcome these obstacles and provide effective treatment, it is crucial to understand the causes of skin cancer, how cells grow and divide, factors that affect cell growth, and how drug resistance occurs. In this review, we have explained various therapeutic approaches for SC treatment via ligands, targeted photosensitizers, natural and synthetic drugs for the treatment of SC, an epigenetic approach for management of melanoma, photodynamic therapy, and targeted therapy for BRAF-mutated melanoma. This article also provides a detailed summary of the various natural drugs that are effective in managing melanoma and reducing the occurrence of skin cancer at early stages and focuses on the current status and future prospects of various therapies available for the management of skin cancer.

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

In this report, we propose a novel strategy for the photodynamic approach to the treatment of melanoma, aiming to mitigate the excessive absorption and consequent thermal effects. The cornerstone of this approach is an innovative structured illumination technique that optimizes light delivery to the tissue. The methodology of this in silico study involves the development of an optical model of human skin with the presence of melanoma and an accurate simulation technique of photon transport within the complex turbid scattering medium. To assess the effectiveness of our proposed strategy, we introduced a cost function reflecting the irradiated volume and optical radiation absorption within the target area/volume occupied by malformation. By utilizing the cost function, we refine the offset illumination parameters for a variety of target system parameters, ensuring increased efficiency of photodynamic therapy. Our computer simulation results introduce a promising new path towards improved photodynamic melanoma treatments, potentially leading to better therapeutic outcomes and reduced side effects. Further experimental validation is needed to confirm these theoretical advancements, which could contribute towards revolutionizing current melanoma photodynamic treatment methodologies.

Cholangiocarcinoma (CCA) is a disease characterized by insidious clinical manifestations and challenging to diagnose. Patients are usually diagnosed at an advanced stage and miss the opportunity for radical surgery. Therefore, effective palliative therapy is the main treatment approach for unresectable CCA. Current common palliative treatments include biliary drainage, chemotherapy, radiotherapy, targeted therapy and immunotherapy. However, these treatments only offer limited improvement in quality of life and survival. Photodynamic therapy (PDT) is a novel local treatment method that is considered a safe tumor ablation method for numerous cancers. It has shown good efficacy in various studies of CCA and is expected to become an important treatment for CCA. In the present study, the mechanisms of PDT in the treatment of CCA were systematically explored and the progress in the research of photosensitizers was discussed. The current study focused on the various PDT protocols and their therapeutic effects in CCA, with the objective of providing a new horizon for future research and clinical applications of PDT in the treatment of CCA.

Research on the development of photodynamic therapy for the treatment of brain tumors has shown promise in the treatment of this highly aggressive form of brain cancer. Analysis of both in vivo studies and clinical studies shows that photodynamic therapy can provide significant benefits, such as an improved median rate of survival. The use of photodynamic therapy is characterized by relatively few side effects, which is a significant advantage compared to conventional treatment methods such as often-used brain tumor surgery, advanced radiotherapy, and classic chemotherapy. Continued research in this area could bring significant advances, influencing future standards of treatment for this difficult and deadly disease.

Most photosensitizers of interest for photodynamic therapy-especially porphyrinoids and chlorins-are hydrophobic. To circumvent this difficulty, the use of nanocarriers is an attractive strategy. In this perspective, we have developed highly water-soluble and biocompatible fluorescent organic nanoparticles (FONPs) made from citric acid and diethyltriamine which are then activated by ethlynene diamine as nanoplatforms for efficient photosensitizers (PSs). Purpurin 18 (Pp18) was selected as a biosourced chlorin photosensitizer combining the efficient single oxygen generation ability and suitable absorption in the biological spectral window. The simple reaction of activated FONPs with Pp18, which contains a reactive anhydride ring, yielded nanoparticles containing both Pp18 and Cp6 derivatives. These functionalized nanoparticles combine solubility in water, high singlet oxygen generation quantum yield in aqueous media (0.72) and absorption both in the near UV region (FONPS) and in the visible region (Soret band approximately 420 nm as well as Q bands at 500 nm, 560 nm, 660 nm and 710 nm). The functionalized nanoparticles retain the blue fluorescence of FONPs when excited in the near UV region but also show deep-red or NIR fluorescence when excited in the visible absorption bands of the PSs (typically at 520 nm, 660 nm or 710 nm). Moreover, these nanoparticles behave as efficient photosensitizers inducing colorectal cancer cell (HCT116 and HT-29 cell lines) death upon illumination at 650 nm. Half maximal inhibitory concentration (IC50) values down to, respectively, 0.04 and 0.13 nmol/mL were observed showing the potential of FONPs[Cp6] for the PDT treatment of cancer. In conclusion, we have shown that these novel biocompatible nanoparticles, which can be elaborated from biosourced components, both show deep-red emission upon excitation in the red region and are able to produce singlet oxygen with high efficiency in aqueous environments. Moreover, they show high PDT efficiency on colorectal cancer cells upon excitation in the deep red region. As such, these functional organic nanoparticles hold promise both for PDT treatment and theranostics.

Warts are caused by human papillomavirus (HPV) infection and can involve multiple parts of skin and mucosa, of which periungual and subungual warts are the most difficult to treat. Periungual or subungual wart is verruca vulgaris growing around or under the fingernail, destroying and deforming the nail and nail bed. Currently, liquid nitrogen cryotherapy and CO2 laser are often used for the treatment. Clinically, few doctors routinely use photodynamic therapy (PDT) to treat viral warts. We used PDT combined with liquid nitrogen cryotherapy and curettage to successfully treat a case of intractable periungual and subungual warts.

Nanotechnology-based phototherapies have drawn interest in the fight against cancer because of its noninvasiveness, high flexibility, and precision in terms of cancer targeting and drug delivery based on its surface properties and size. Phototherapy has made remarkable development in recent decades. Approaches to phototherapy, which utilize nanomaterials or nanotechnology have emerged to contribute to advances around nanotechnologies in medicine, particularly for cancers. A brief overviews of the development of photodynamic therapy as well as its mechanism in cancer treatment is provided. We emphasize the design of novel nanoparticles utilized in photodynamic therapy while summarizing the representative progress during the recent years. Finally, to forecast important future research in this area, we examine the viability and promise of photodynamic therapy systems based on nanoparticles in clinical anticancer treatment applications and briefly make mention of the elimination of all reactive metabolites pertaining to nano formulations inside living organisms providing insight into clinical mechanistic processes. Future developments and therapeutic prospects for photodynamic treatments are anticipated. Our viewpoints might encourage scientists to create more potent phototherapy-based cancer therapeutic modalities. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.