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In photodynamic therapy (PDT) treatment, heavy-atom-free photosensitizers (PSs) are a great source of singlet oxygen photosensitizer. Reactive oxygen species (ROS) are produced by an energy transfer from the lowest energy triplet excited state to the molecular oxygen of cancer cells. To clarify the photophysical characteristics in the excited states of a few experimentally identified thionated (>C=S) molecules and their oxygenated congeners (>C=O), a quantum chemical study is conducted. This study illustrates the properties of the excited states in oxygen congeners that render them unsuitable for PDT treatment. Concurrently, a hierarchy is presented based on the utility of the lowest-energy triplet excitons of thionated compounds. Their non-radiative decay rates are calculated for reverse-ISC and inter-system crossover (ISC) processes. In addition, the vibronic importance of C=O and C=S bonds is clarified by the computation of the Huang–Rhys factor, effective vibrational mode, and reorganization energy inside the Marcus–Levich–Jörtner system. ROS generation in thionated PSs exceeds their oxygen congeners as kf ≪ kISC, where radiative decay rate is designated as kf. As a result, the current work offers a calculated strategy for analyzing the effectiveness of thionated photosensitizers in PDT. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to assess the impact of photodynamic therapy (PDT) on the oral health-related quality of life (OHRQoL) among denture stomatitis patients with implant overdenture prostheses (IODs). Materials and Methods: The patients were recruited from a specialist dental practice according to selection criteria. The Candida spp. were identified and confirmed by the microbiological culture technique. Candida counts were estimated as colony-forming units (CFU/ml) at baseline, 15, 30, and 60 days. PDT was carried out twice a week with 72 h intervals for a period of 4 weeks. A structured questionnaire was used for data collection. It included the demographic details of the patients, including age, gender, education, marital and socioeconomic status (SES), oral habits, and smoking status. In addition, the Oral Health Impact Profile-EDENT (OHIP-EDENT) scale was added to assess the OHRQoL of all patients before and after PDT treatment. The data were analysed using descriptive statistics, the t-test and the Shapiro-Wilk test; statistical signifcance was set at p < 0.05. Results: At baseline, the overall mean Candida CFU/ml were quite high in the implant overdenture (IODs) samples, 37.12 ± 15.8, as compared to palatal mucosa samples with 5.1 ± 2.3. After PDT treatment, a statistically significant reduction was noted in the mean Candida CFU/ml on both surfaces at all follow-up visits. It was observed that all domains of OHIP-EDENT except for physical disability and handicap showed statistically significant improvement in mean scores after PDT treatment. FL, P1, P2, D2, and D3 had statistically significant mean score improvements of 2.2, 3.1, 2.2, 1.4, and 0.7, respectively. Furthermore, after PDT treatment, the total OHIP-EDENT score showed a statistically significant improvement of 11.6. Conclusion: PDT treatment has a positive impact on the OHRQoL for patients with denture stomatitis. It can be used as an effective treatment option for the treatment of denture stomatitis in IOD patients. [ABSTRACT FROM AUTHOR]

In this paper, we explore the molecular basis of combining photodynamic therapy (PDT), a light-triggered targeted anticancer therapy, with the traditional chemotherapeutic properties of the well-known cytotoxic agent gemcitabine. A photosensitizer prerequisite is significant absorption of biocompatible light in the visible/near IR range, ideally between 600 and 1000 nm. We use highly accurate multiconfigurational CASSCF/MS-CASPT2/MM and TD-DFT methodologies to determine the absorption properties of a series of gemcitabine derivatives with the goal of red-shifting the UV absorption band toward the visible region and facilitating triplet state population. The choice of the substitutions and, thus, the rational design is based on important biochemical criteria and on derivatives whose synthesis is reported in the literature. The modifications tackled in this paper consist of: (i) substitution of the oxygen atom at O2 position with heavier atoms (O → S and O → Se) to red shift the absorption band and increase the spin–orbit coupling, (ii) addition of a lipophilic chain at the N7 position to enhance transport into cancer cells and slow down gemcitabine metabolism, and (iii) attachment of aromatic systems at C5 position to enhance red shift further. Results indicate that the combination of these three chemical modifications markedly shifts the absorption spectrum toward the 500 nm region and beyond and drastically increases spin–orbit coupling values, two key PDT requirements. The obtained theoretical predictions encourage biological studies to further develop this anticancer approach. [ABSTRACT FROM AUTHOR]

BackgroundPort wine birthmark (PWB) is a congenital vascular malformation of the skin. Pulsed dye laser (PDL) is the "gold standard" for the treatment of PWB globally. Hematoporphyrin monomethyl ether (HMME or hemoporfin)-mediated photodynamic therapy (HMME-PDT) has emerged as the first choice for PWB treatment, particularly for young children, in many major hospitals in China during the past several decades.AimTo evaluate whether HMME-PDT is superior to PDL by comparing the clinical efficacies of both modalities.MethodPubMed records were searched for all relevant studies of PWB treatment using PDL (1988-2023) or HMME-PDT (2007-2023). Patient characteristics and clinical efficacies were extracted. Studies with a quartile percentage clearance or similar scale were included. A mean color clearance index (CI) per study was calculated and compared among groups. An overall CI (C0 ), with data weighted by cohort size, was used to evaluate the final efficacy for each modality.ResultA total of 18 HMME-PDT studies with 3910 patients in China were eligible for inclusion in this analysis. Similarly, 40 PDL studies with 5094 patients from nine different countries were eligible for inclusion in this analysis. Over 58% of patients in the HMME-PDT studies were minors (

BackgroundPhotodynamic therapy (PDT) efficacy is determined in part by the concentration of photosensitizer (PS) at the treatment site. The blood-brain barrier (BBB) poses a significant limitation on the transport of PS into the post-operative resection region where brain tumors most often recur. Macrophages (Ma), as opposed to free or nanoparticle bound agents, are known to actively migrate to and around tumors, and can therefore be used as delivery vectors for both drugs and photosensitizers.MethodsMouse Ma (RAW264.7) and F98 rat glioma cells were used in all experiments along with the photosensitizer AlPcS2a. Mitomycin-treated Ma were loaded with photosensitizer (PS) and mixed with glioma cells, forming hybrid spheroids. F98 spheroids were incubated with supernatants derived from PS-loaded Ma (MaPS). Light treatment (PDT) was administered at various radiant exposures from a 670 nm diode laser. The growth of both types of spheroids was evaluated by measurement of spheroid volume after 14 days in culture.ResultsPDT on F98 cell spheroid cultures, mediated by either free or PS-released from Ma, demonstrated a significant growth inhibition with supernatants harvested after 4 and 24 h. A significant PDT-induced growth inhibition was demonstrated in the MaPS/F98 hybrid spheroid experiments.ConclusionSince the efficacy of PDT, mediated by either free or released photosensitizer was comparable, the uptake and released photosensitizer was not degraded. MaPS, incorporated in hybrid tumor spheroids also mediated effective PDT. These results indicate that Ma have potential as an effective vector for photosensitizer delivery to resected brain tumors.

INTRODUCTION: Photodynamic therapy (PDT) has shown substantial benefit in the treatment of choroidal hemangioma (CH) in recent years. This report describes the use of PDT with overlapping spots in a patient with Sturge-Weber syndrome (SWS) and large circumscribed CH. CASE PRESENTATION: A 9-year-old girl with SWS and a history of glaucoma in her left eye was referred to a retina clinic for possible macular changes. Examination revealed decreased vision in the left eye, pigmentary changes in the macula, and choroidal thickening in the posterior pole. After being lost to follow-up for 2 years, the patient returned with further vision deterioration with best-corrected visual acuity (BCVA) of 20/150 and new subretinal fluid (SRF). Imaging findings were consistent with a diagnosis of CH and SRF. PDT with verteporfin was initiated on the entire area with multiple overlapping spots, resulting in resolution of SRF and improvement in visual acuity and choroidal contour. At 18-month post-treatment, the patients BCVA was 20/25 with no recurrence of SRF or increased choroidal thickening. Significant pigmentary changes and subretinal hyper-reflective material were observed in the OCT of the treated area. CONCLUSION: Multiple overlapping laser spots of PDT can result in longstanding regression of large circumscribed CH in a patient with SWS with excellent final visual acuity. However, significant subretinal changes may also result following this method of treatment.

Port-wine stains (PWS) are congenital vascular malformations characterized by capillary malformations that persist and often darken over time. Traditional treatment methods, including laser therapy, have shown varying degrees of effectiveness and can be associated with significant side effects. Hematoporphyrin Monomethyl Ether-Photodynamic Therapy (HMME-PDT) has emerged as a promising alternative, offering targeted treatment with potentially fewer adverse effects. This paper aims to evaluate the clinical efficacy and potential of HMME-PDT as a treatment strategy for PWS. It provides a comprehensive review of the literature and clinical investigations to assess the application and outcomes of HMME-PDT in treating PWS. Briefly introduce the nature of PWS, innovations and challenges in treatment, the mechanism of HMME-PDT, clinical effectiveness and sonographic appearance, safety and long-term effects, and challenges and suggestions for optimizing treatment. The review highlights the mechanism by which HMME-PDT works, focusing on its ability to target abnormal blood vessels selectively. Clinical evaluations included clinical and sonographic assessments to determine the efficacy of the treatment. The findings revealed significant improvements in the clinical appearance and sonographic features of vascular lesions following HMME-PDT. The paper also discusses the utility of dermoscopy in HMME-PDT applications, factors affecting treatment efficacy, the impact of thermal assistance on the effectiveness of PDT, and the management of adverse reactions through proper nursing care. The review underscores the considerable potential of HMME-PDT as an effective treatment for PWS, noting its promising outcomes in clinical and sonographic assessments. However, it also emphasizes the need for further research to standardize treatment protocols and assess long-term outcomes. [ABSTRACT FROM AUTHOR]

Near‐infrared photosensitizers are valuable tools to improve treatment depth in photodynamic therapy (PDT). However, their low singlet oxygen (1O2) generation ability, indicated by low 1O2 quantum yield, presents a formidable challenge for PDT. To overcome this challenge, the heptamethine cyanine was decorated with biocompatible S (Scy7) and Se (Secy7) atom. We observe that Secy7 exhibits a redshift in the main absorption to ~840 nm and an ultra‐efficient 1O2 generation capacity. The emergence of a strong intramolecular charge transfer effect between the Se atom and polymethine chain considerably narrows the energy gap (0.51 eV), and the heavy atom effect of Se strengthens spin–orbit coupling (1.44 cm−1), both of which greatly improved the high triplet state yield (61 %), a state that determines the energy transfer to O2. Therefore, Secy7 demonstrated excellent 1O2 generation capacity, which is ~24.5‐fold that of indocyanine green, ~8.2‐fold that of IR780, and ~1.3‐fold that of methylene blue under low‐power‐density 850 nm irradiation (5 mW cm−2). Secy7 exhibits considerable phototoxicity toward cancer cells buried under 12 mm of tissue. Nanoparticles formed by encapsulating Secy7 within amphiphilic polymers and lecithin, demonstrated promising antitumor and anti‐pulmonary metastatic effects, exhibiting remarkable potential for advancing PDT in deep tissues. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) often faces challenges such as oxygen dependence and limited tumour specificity. We report a tumour-targeting photosensitizer (PS), RUCXB, which enhances uptake by cancer cells by targeting overexpressed cyclooxygenase-2 enzyme in tumours. RUCXB also reduces oxygen dependence via a type I PDT mechanism and achieves a strong therapeutic effect through the synergistic induction of ferroptosis and apoptosis. This work presents a reliable strategy for developing potent PSs with enhanced PDT efficacy, tumour selectivity, and diminished oxygen dependence. [ABSTRACT FROM AUTHOR]

This study investigates novel zinc and indium phthalocyanines with Schiff base and sulphur moieties, focusing on their potential for cancer therapy and antimicrobial applications. It explores the effectiveness of photochemical and sono-photochemical methods to enhance singlet oxygen production, which is crucial for photodynamic therapy. The synthesized complexes in this study demonstrated high singlet oxygen quantum yields, with D3 (ZnPc) and D4 (InPc) showing ΦΔPDT values of 0.71 and 0.75, and ΦΔSPDT values of 0.91 and 0.94, respectively. Furthermore, the evaluation for biological properties revealed that both D3 and D4 exhibit significant antidiabetic properties, DPPH radical scavenging activity, DNA cleavage, antimicrobial activity, biofilm inhibition, and microbial cell viability impacts, both with and without photodynamic therapy. Notably, D3 and D4 achieved antimicrobial cell viability inhibition rates of 84.67 ± 4.67% and 98.32 ± 5.96%, respectively, showcasing their effectiveness in photodynamic antimicrobial therapy. Overall, the study highlights the potential of these phthalocyanine complexes as advanced photosensitizers, with strong singlet oxygen generation and promising biological activities, paving the way for future therapeutic applications. [ABSTRACT FROM AUTHOR]

[Display omitted] Non-invasive and efficient photodynamic therapy (PDT) holds great promise to circumvent resistance to traditional osteosarcoma (OS) treatments. Nevertheless, high-power PDT applied in OS often induces photothermogenesis, resulting in normal cells rupture, sustained inflammation and irreversible vascular damage. Despite its relative safety, low-power PDT fails to induce severe DNA damage for insufficient reactive oxygen species (ROS) production. Herein, a non-ROS-dependent DNA damage-sensitizing strategy is introduced in low-power PDT to amplify the therapeutic efficiency of OS, where higher apoptosis is achieved with low laser power. Inspired by the outstanding DNA damage performance of tannic acid (TA), TA-based metal phenolic networks (MPNs) are engineered to encapsulate hydrophobic photosensitizer (purpurin 18) to act as DNA damage-sensitized nanosynergists (TCP NPs). Specially, under low-power laser irradiation, the TCP NPs can boost ROS instantly to trigger mitochondrial dysfunction simultaneously with upregulation of DNA damage levels triggered by TA to reinforce PDT sensitization, evoking potent antitumor effects. In addition, TCP NPs exhibit long-term retention in tumor, greatly benefiting sustained antitumor performances. Overall, this study sheds new light on promoting the sensitivity of low-power PDT by strengthening DNA damage levels and will benefits advanced OS therapy. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) presents a promising approach for combating periodontitis, an infectious disease triggered by bacteria. However, the hypoxic environment within periodontal pockets poses challenges for PDT efficacy. In this study, novel purine‐based C^N ligands are utilized to develop Ir(III) complexes with enhanced reactive oxygen species (ROS) generation capacity for periodontitis treatment. The type I/II PDT performance of Ir(III) is greatly enhanced by the purine ligands, which leads to potent bactericidal and biofilm elimination efficacy. In a rat model of periodontitis, local application of these purine‐based Ir(III) complexes effectively achieves antibacterial and anti‐inflammatory effects while promoting tissue repair under clinical luminaire exposure. This PDT strategy utilizing purine‐based Ir(III) complexes circumvents the need for antibiotics and surgical intervention, emerging as a promising, non‐invasive approach for managing periodontitis. [ABSTRACT FROM AUTHOR]

The development of durable photosensitizers is pivotal for advancing phototherapeutic applications in biomedicine. Here, we introduce a core‐shell azobenzene‐spiropyran structure on gold nanoparticles, engineered to enhance singlet oxygen generation. These nano‐photosensitizers exhibit increased structural stability and thermal resistance, as demonstrated by slowed O−N−C bond recombination dynamics via in‐situ Raman spectroscopy. Notably, the in‐situ formation of merocyanine and a light‐induced compact shell arrangement extend its half‐life from 47 minutes to over 154 hours, significantly boosting singlet oxygen output. The nano‐photosensitizer also shows high biocompatibility and notably inhibits tau protein aggregation in neural cells, even with phosphatase inhibitors. Further, it promotes dendritic growth in neuro cells, doubling typical lengths. This work not only advances chemical nanotechnology but also sets a foundation for developing long‐lasting phototherapy agents for treating neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Self‐assembly has proven to be one of the effective methods for the formation of nanoscale therapeutics without the need to use nanodelivery systems. Such minimal models of supramolecular systems formed from amphiphilic photosensitizers (PS) have recently emerged as a new class of photoactive systems, providing unique and in some cases superior activities. Although the mechanism of photogenerated reactive oxygen species (ROS) in such systems is studied and to a certain extent understood, there are very limited studies investigating the influence of intricate environmental factors, including those occurring in the cellular environment, on the self‐assembly and thus the activity of the system. Understanding the optimal conditions for the formation of active PS aggregates is an important area of research in the field of photodynamic therapy (PDT), as it is directly linked to the optimal treatment dose. In this study, we describe the synthesis, self‐assembly properties, photophysical characterization, and photobiological efficacy of structurally closely related low‐symmetry phthalocyanine derivatives. Studying the decay behavior of the PS fluorescence lifetime in the presence of molecular crowders and different bacterial strains, we found that certain derivatives exhibited adaptive behavior and change in activity, while others demonstrated non‐adaptive characteristics. [ABSTRACT FROM AUTHOR]

The study aimed to compare the effectiveness between Hiporfin-photodynamic therapy (PDT) and loop electrosurgical excision procedure (LEEP) in treating cervical high-grade squamous intraepithelial lesion (HSIL). We conducted a retrospective analysis of 104 women diagnosed with cervical HSIL at our hospital from April 2019 to July 2023. With 1:1 matched case-control, 52 cases received Hiporfin-PDT and 52 cases underwent LEEP. All PDT-treated cases received Hiporfin (2 mg/kg) I.V. and a diode laser at a wavelength of 630-nm. T-test, Chi-square test, Fisher's exact test, and Yates's correction for continuity were conducted for statistical. A P value < 0.05 was considered significant. The complete response (CR) post-PDT at 3rd-6th months,10th-12th months and 24th months was in 98.1% (51/52),100.0% (45/45) and 100.0% (22/22) patients respectively, compared to 98.1% (51/52), 100.0% (46/46) and 100.0% (24/24) patients respectively after LEEP. HPV clearance rates after PDT at 3rd-6th months,10th-12th months and 24th months was 76.9% (40/52), 88.9% (40/45) and 95.5% (21/22) respectively, compared to 69.2% (36/52), 93.5% (43/46) and 95.8% (23/24) respectively after LEEP, with no significant difference between the two groups (P = 0.508, P = 0.687 and P = 1.000, respectively). Postoperative complications in the PDT group were tolerable. The cure rates and HPV eradication of Hiporfin-PDT were comparable with that of LEEP in the management of cervical HSIL. Hiporfin-PDT may serve an alternative method for organ-saving in cervical HSIL. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) stands out as a highly promising modality for tumor treatment, yet previous works have primarily centered around either boosting the production of reactive oxygen species (ROS) in tumor tissues or restricting it in normal tissues. The current challenge lies in the urgent need to achieve precise modulation of ROS production by simultaneously controlling both aspects. To achieve this goal, a precise PDT platform through a “locking‐unlocking‐boosting” ROS production strategy is presented, in which the generation of ROS is modulated by bidirectionally regulating the upconversion luminescence (UCL) of lanthanide‐doped nanoparticles (LnNPs), thus ROS production is “locked” in normal tissues but “boosted” in tumor tissues. In detail, by introducing an energy acceptor BHQ3, the UCL is initially quenched to prevent Chlorin e6 (Ce6) from generating ROS. However, under the tumor microenvironment with overexpressed miR‐21, LnNPs are sequestered from BHQ3 to “unlock” ROS generation and then assembled with QDs@B2, which functions as an antenna to sensitize LnNPs luminescence, to further “boost” ROS generation. With the assistance of spherical nucleic acids, this therapeutic agent effectively traverses the blood‐brain barrier (BBB), enabling efficient PDT for glioblastoma. [ABSTRACT FROM AUTHOR]

Upconversion nanoparticles (UCNPs) have been used as a potential nanocarrier for photosensitizers (PSs), which have demonstrated a great deal of promise in achieving an effective photodynamic therapy (PDT) for deep-seated tumors. However, overcoming biological barriers to achieve mitochondria-targeted PDT remains a major challenge. Herein, CD44- and mitochondria-targeted photodynamic nanosystems were fabricated through the self-assembly of hyaluronic acid-conjugated-methoxy poly(ethylene glycol)-diethylenetriamine-grafted-(chlorin e6-dihydrolipoic acid-(3-carboxypropyl)triphenylphosphine bromide) polymeric ligands (HA-c-mPEG-Deta-g-(Ce6-DHLA-TPP)) and NaErF4:Tm@NaYF4 core–shell UCNPs (termed CMPNs). The CMPNs presented ideal physiological stability, a good drug loading capacity and an improved capacity for the generation of singlet oxygen (1O2) based on the FRET mechanism. Significantly, confocal images revealed that CMPNs not only facilitated cellular uptake through CD44-receptor-targeted endocytosis, subsequently enabling rapid evasion from endo-lysosomal sequestration, but also specifically targeted mitochondria, ultimately inducing a profound disruption of mitochondrial membrane potential, which triggered apoptosis upon laser irradiation, thereby significantly enhancing the therapeutic effect. Furthermore, in vitro antitumor experiments further confirmed the substantial enhancement in cancer cell killing efficiency achieved by treating with CMPNs upon near-infrared (NIR) laser irradiation. This innovative approach holds promise for the development of NIR-laser-activated photodynamic nanoagents specifically designed for mitochondria-targeted PDT, thus addressing the limitations of the current PDT treatments. [ABSTRACT FROM AUTHOR]

Ferroptosis is considered an effective method to overcome drug-resistant tumors. This study aims to use three FDA-approved biological materials, human serum albumin, D-α-tocopherol succinate, and indocyanine green, to construct a novel biocompatible nanomaterial named HTI-NPs, exploring its effect in drug-resistant breast cancer (MCF-7/ADR cells). The research results indicate that HTI-NPs can selectively inhibit the proliferation of MCF-7/ADR cells in vitro , accompanied by upregulating transferrin receptor, generating reactive oxygen species, and downregulating glutathione peroxidase 4. Under laser irradiation, HTI-NPs can promote ferroptosis by inhibiting glutathione expression through photodynamic therapy. Notably, HTI-NPs exhibit good inhibitory effects on MCF-7/ADR xenograft tumors in vivo. In conclusion, HTI-NPs represent a biocompatible nanomaterial that induces ferroptosis, providing new insights and options for treating drug-resistant breast cancer. [ABSTRACT FROM AUTHOR]

Synthesis of BODIPY oligomers has attracted increasing attention due to their intriguing properties and promising applications. Significant progress has been made to synthesize BODIPY oligomers via post‐functionalization, either single‐bond linked or fully conjugated. This concept article highlights the recent developments of BODIPY oligomers, including the synthetic routes, their photophysical properties and applications in the areas of NIR light absorbing dye, photodynamic therapy, and bioimaging etc. [ABSTRACT FROM AUTHOR]

Doping of polycyclic conjugated hydrocarbons (PCHs) with sulfur atoms is becoming more and more important as a means of creating unique functional materials. Recently, thiophene‐containing multiple helicenes have garnered enormous attention due to their intriguing electronic and (chir)optical properties compared with carbohelicenes. However, the efficient synthesis of thiopyran‐containing multiple helicenes and the underlying sulfur doping mechanisms are rather unexplored. Herein, the synthesis and structural analysis of a thiopyran‐containing double [7]helicene 3 are reported. X‐ray crystallographic analysis reveals 3 and its dication with C2‐symmetric propeller‐shape structures and compact interactions in the solid state. 3 exhibits deep‐red to near‐infrared (NIR) fluorescence emission. Tunable aromaticity of the central benzene ring and thiopyran rings is found by chemical oxidation, which is further confirmed by nucleus‐independent chemical shift (NICS), anisotropy of the induced current density (ACID) and harmonic oscillator model of aromaticity (HOMA) analysis. Furthermore, the chiral and photosensitizing characters of 3 are investigated. The excellent deep‐red to NIR fluorescence, circularly polarized luminescence (CPL) and photosensitizing activities suggest that 3 can be used as an outstanding photosensitizer in photodynamic therapy (PDT) and bioimaging, especially paving the way for future CPL‐PDT and CPL‐bio‐probe applications. [ABSTRACT FROM AUTHOR]

Photodynamic therapy and ferroptosis induction have risen as vanguard oncological interventions, distinguished by their precision and ability to target vulnerabilities in cancer cells. Photodynamic therapy's non-invasive profile and selective cytotoxicity complement ferroptosis' unique mode of action, which exploits iron-dependent lipid peroxidation, offering a pathway to overcome chemoresistance with lower systemic impact. The synergism between photodynamic therapy and ferroptosis is underscored by the depletion of glutathione and glutathione peroxidase four inhibitions by photodynamic therapy-induced reactive oxygen species, amplifying lipid peroxidation and enhancing ferroptotic cell death. This synergy presents an opportunity to refine cancer treatment by modulating redox homeostasis. Porphyrin-based nanoscale metal-organic frameworks have unique hybrid structures and exceptional properties. These frameworks can serve as a platform for integrating photodynamic therapy and ferroptosis through carefully designed structures and functions. These nanostructures can be engineered to deliver multiple therapeutic modalities simultaneously, marking a pivotal advance in multimodal cancer therapy. This review synthesizes recent progress in porphyrin-modified nanoscale metal-organic frameworks for combined photodynamic therapy and ferroptosis, delineating the mechanisms that underlie their synergistic effects in a multimodal context. It underscores the potential of porphyrin-based nanoscale metal-organic frameworks as advanced nanocarriers in oncology, propelling the field toward more efficacious and tailored cancer treatments. [ABSTRACT FROM AUTHOR]

Background: Near-infrared photoimmunotherapy (NIR-PIT) is an emerging cancer treatment technology that combines the advantages of optical technology and immunotherapy to provide a highly effective, precise, and low side-effect treatment approach. The aim of this study is to visualize the scientific results and research trends of NIR-PIT based on bibliometric analysis methods. Methods: The Web of Science Core Collection (WoSCC) database was searched in August 2024 for relevant publications in the field of NIR-PIT. Data were analyzed using mainly CiteSpace and R software for bibliometric and visual analysis of the country/region, authors, journals, references and keywords of the publications in the field. Results: A total of 245 publications were retrieved, including articles (n = 173, 70.61%) and reviews (n = 72, 29.39%). The annual and cumulative number of publications increased every year. The highest number of publications was from the United States (149, 60.82%), followed by Japan (70, 28.57%) and China (33, 13.47%). The research institution with the highest number of publications was National Institutes of Health (NIH)-USA (114, 46.53%). Kobayashi H (109) was involved in the highest number of publications, Mitsunaga M (211) was the most frequently cited in total. CANCERS (17) was the most frequently published journal, and NAT MED (220) was the most frequently co-cited journal. The top 10 keywords include near-infrared photoimmunotherapy (166), photodynamic therapy (61), monoclonal antibody (58), in vivo (50), cancer (46), expression (31), breast cancer (27), enhanced permeability (24), antibody (23), growth factor receptor (16). Cluster analysis based on the co-occurrence of keywords resulted in 13 clusters, which identified the current research hotspots and future trends of NIR-PIT in cancer treatment. Conclusion: This study systematically investigated the research hotspots and development trends of NIR-PIT in cancer treatment through bibliometric and visual analysis. As an emerging strategy, the research on the application of NIR-PIT in cancer treatment has significantly increased in recent years, mainly focusing on the targeting, immune activation mechanism, and treatment efficacy in solid tumors has received extensive attention. Future studies may focus on improving the efficacy and safety of NIR-PIT in cancer treatment, as well as developing novel photosensitizers and combination therapeutic regimens, and exploring the efficacy of its application in a wide range of solid tumors, which will provide an important reference and guidance for the application of NIR-PIT in clinical translation. [ABSTRACT FROM AUTHOR]

Tin oxide (SnO2) nanoparticles doped with europium impurities were synthesized, and their ability to generate singlet oxygen and hydroxyl radicals was investigated for photodynamic therapy. They were detected using Anthracene and methylene blue reagentsThe process involved chemical synthesis of nanoparticles, followed by analysis of their structural properties and characteristics using X-ray diffraction (XRD), Field emission scanning electron microscopy (FE-SEM), and Fourier transform Infrared spectroscopy (FTIR). Additionally, the nanoparticles' optical properties were studied using Photoluminescence spectroscopy (PL) for potential tumor applications. The analysis of the results shows that the prepared nanoparticles have a tetragonal structure, with a size of 14 nm. Additionally, when excited at a wavelength of 275 nm, they exhibit emission peaks at 388, 412, 481, 667, and 735 nm. Nanoparticles not only have the appropriate photoluminescence spectrum needed for photodynamic therapy, but they also exhibit a strong afterglow. These nanoparticles can serve as an effective light source for treating deep tumors. To achieve this, the nanoparticles are stimulated outside the body and then used as a light source. In this study, UV and X-rays were employed to stimulate the nanoparticles and investigate their photodynamic therapy properties. The findings suggest that SnO2: Eu nanoparticles show promise as a novel and cost-effective treatment for deep tumor photodynamic therapy. [ABSTRACT FROM AUTHOR]

A covalent assembly strategy was developed to construct a gold nanocluster-based nano-assembly (AuNCNA) in a controllable manner, using Au8 nanocluster as node and 5,10,15,20-tetra(4-alkynylphenyl)porphine (TEPP) as ligand. Subsequently, the tripeptide arginine glycine aspartic acid (RGD) peptide is further modified via clicking reaction to build a multi-functional nanoplatform (AuNCNA@RGD) that can integrate the targeted fluorescence imaging and efficient photodynamic therapy (PDT). The strong interregulation of Au8 nanocluster and TEPP results in AuNCNA@RGD exhibiting three distinct advantages: (i) TEPP plays an important role in stabilizing the Au8 nanocluster and keeping the active site fixed within the framework, thereby enhancing stability of Au8 nanocluster; (ii) Au8 nanocluster possess adjustable energy level, which can accelerate the transfer of photogenerated charge and prevent the recombination of electrons and holes, thus improving the photosensitivity of TEPP for PDT; (iii) AuNCNA exhibits bright fluorescence emission that facilitates RGD-assisted targeted tumor imaging. This work expands the construction method of AuNC assembly, and this assembly method is versatile and can flexibly transform different organic ligands to construct various AuNC-based functional nanomaterials. [ABSTRACT FROM AUTHOR]

Protoporphyrin IX (PpIX)‐based photodynamic therapy (PDT) has shown limited efficacy in nonmuscle‐invasive bladder cancer (NMIBC). To improve PDT efficacy, we developed singlet oxygen‐cleavable prodrugs. These prodrugs, when combined with PpIX‐PDT, induce cancer cell death through both PDT and drug release mechanisms. Inhibition of PpIX efflux was reported to be an effective strategy to improve PpIX‐PDT in certain cancer cells. Our main goal was to investigate whether adding an efflux inhibitor to the combination of PpIX and prodrugs can improve the PpIX levels in bladder cancer cells and the release of active drugs, thus improving the overall efficacy of the treatment. We treated bladder cancer cell lines with lapatinib and evaluated intracellular PpIX fluorescence, finding significantly increased accumulation. Combining lapatinib with prodrugs led to significantly reduced cell viability compared to prodrugs or PpIX‐PDT alone. The effect of lapatinib depended on the expression level of the efflux pump in bladder cancer cells. Interestingly, lapatinib increased paclitaxel (PTX) prodrug uptake by threefold compared to prodrug alone. Adding an efflux inhibitor (e.g., lapatinib) into bladder instillation solutions could be a straightforward and effective strategy for NMIBC treatment, particularly in tumors expressing efflux pumps, with the potential for clinical translation. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus is a global challenge to the clinical field and food industry. Therefore, the development of antimicrobial photodynamic therapy (aPDT) has become one of the valuable methods to control this pathogen. The antibacterial activity of photoinactivation by erythrosine (Ery) against S. aureus has been reported, but its modes of action are unclear. This study aimed to employ a proteomic approach to analyze modes of action of Ery‐aPDT against S. aureus. We determined the antibacterial effect by Ery‐aPDT assays, quantified reactive oxygen species (ROS) and injury to the cell membrane, and determined protein expression using a proteomic approach combined with bioinformatic tools. Ery‐aPDT was effective in reducing S. aureus to undetectable levels. In addition, the increment of ROS accompanied the increase in the reduction of cell viability, and damage to cellular membranes was shown by sublethal injury. In proteomic analysis, we found 17 differentially expressed proteins. These proteins revealed changes mainly associated with defense to oxidative stress, energy metabolism, translation, and protein biosynthesis. Thus, these results suggest that the effectiveness of Ery‐aPDT is due to multi‐targets in the bacterial cell that cause the death of S. aureus. [ABSTRACT FROM AUTHOR]

5‐Aminolevulinic acid (ALA) is a prodrug for protoporphyrin IX (PpIX)‐mediated photodynamic therapy (PDT) and fluorescence‐guided tumor surgery. We previously reported that lapatinib, a repurposed ABCG2 inhibitor, enhanced ALA‐induced PpIX fluorescence and PDT by blocking ABCG2‐mediated PpIX efflux. In the present study, we evaluated how the variation in ABCG2 activities/protein levels affected tumor cell response to the enhancement of PpIX/PDT by lapatinib and Ko143, an ABCG2 tool inhibitor. ABCG2 activities and protein levels were determined in a panel of human cancer cell lines. Effects of lapatinib and Ko143 on enhancing ALA‐PpIX fluorescence and PDT were evaluated and correlated with tumor cell ABCG2 activities. We found that both lapatinib and Ko143 enhanced ALA‐PpIX fluorescence and PDT in a dose‐dependent manner, although lapatinib exhibited lower efficacy and potency than Ko143 in nearly all cancer cell lines. The EC50 of ABCG2 inhibitors for enhancing ALA‐PpIX and PDT had a positive correlation with tumor cell ABCG2 activities, indicating that tumor cell lines with lower ABCG2 activities were more sensitive to ABCG2 inhibitors for PpIX/PDT enhancement. Our results suggest that, for optimal therapeutic enhancement, the dose of ABCG2 inhibitors needs to be tailored based on the ABCG2 expression/activity in tumors. [ABSTRACT FROM AUTHOR]

It has been 30 years since Photofrin‐PDT was approved for the treatment of bladder cancer in Canada. However, Photofrin‐PDT failed to gain popularity due to bladder complications. The PDT with red light and IV‐administered Photofrin could permanently damage the bladder muscle. We have been developing a new combination strategy of PpIX‐PDT with singlet oxygen‐cleavable prodrugs for NMIBC with minimal side effects, avoiding damage to the bladder muscle layer. PpIX can be excited by either green (532 nm) or red (635 nm) light. Red light could be more efficacious in vivo due to its deeper tissue penetration than green light. Since HAL preferentially produces PpIX in tumors, we hypothesized that illuminating PpIX with red light might spare the muscle layer. PpIX‐PDT was used to compare green and red laser efficacy in vitro and in vivo. The IC50 of in vitro PpIX‐PDT was 18 mW/cm2 with the red laser and 22 mW/cm2 with the green laser. The in vivo efficacy of the red laser with 50, 75, and 100 mW total dose was similar to the same dose of green laser in reducing tumor volume. Combining PpIX‐PDT with prodrugs methyl‐linked mitomycin C (Mt‐L‐MMC) and rhodamine‐linked SN‐38 (Rh‐L‐SN‐38) significantly improved efficacy (tumor volume comparison). PpIX‐PDT or PpIX‐PDT + prodrug combination did not cause muscle damage in histological analysis. Overall, a combination of PpIX‐PDT and prodrug with 635 nm laser is promising for non‐muscle invasive bladder cancer treatment. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a nonscarring cancer treatment in which a pro‐drug (5‐aminolevulinic acid, ALA) is applied, converted into a photosensitizer (protoporphyrin IX, PpIX) which is then activated by visible light. ALA‐PDT is now popular for treating nonmelanoma skin cancer (NMSC), but can be ineffective for larger skin tumors, mainly due to inadequate production of PpIX. Work over the past two decades has shown that differentiation‐promoting agents, including methotrexate (MTX), 5‐fluorouracil (5FU) and vitamin D (Vit D) can be combined with ALA‐PDT as neoadjuvants to promote tumor‐specific accumulation of PpIX, enhance tumor‐selective cell death, and improve therapeutic outcome. In this review, we provide a historical perspective of how the combinations of differentiation‐promoting agents with PDT (cPDT) evolved, including Initial discoveries, biochemical and molecular mechanisms, and clinical translation for the treatment of NMSCs. For added context, we also compare the differentiation‐promoting neoadjuvants with some other clinical PDT combinations such as surgery, laser ablation, iron‐chelating agents (CP94), and immunomodulators that do not induce differentiation. Although this review focuses mainly on the application of cPDT for NMSCs, the concepts and findings described here may be more broadly applicable towards improving the therapeutic outcomes of PDT treatment for other types of cancers. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) initially employed red light, which caused some patients to experience permanent bladder contractions. PDT using the FDA‐approved drug hexaminolevulinate (HAL), which produces protoporphyrin IX (PpIX) in the tumor, showed some promise but has low efficacy in treating non‐muscle‐invasive bladder cancer (NMIBC). We developed singlet oxygen‐activatable prodrugs of two anticancer drugs, paclitaxel and mitomycin C, to enhance the antitumor effect of PpIX‐PDT without producing systemic side effects, by promoting only local release of the active chemotherapeutic agent. Orthotopic NMIBC model was used to compare the efficacy of prodrugs only, PpIX‐PDT, and prodrugs + PpIX‐PDT. 532 nm laser with a total power of 50 mW for 20 min (60 J, single treatment) was used with HAL and prodrugs. Histology and microscopic methods with image analysis were used to evaluate the tumor staging, antitumor efficacy, and local toxicity. Prodrug + PpIX‐PDT produced superior antitumor efficacy than PpIX‐PDT alone with statistical significance. Both PpIX‐PDT alone and combination therapy resulted in mild damage to the bladder epithelium in the normal bladder area with no apparent damage to the muscle layer. Overall, SO‐cleavable prodrugs improved the antitumor efficacy of PpIX‐PDT without causing severe and permanent damage to the bladder muscle layer. [ABSTRACT FROM AUTHOR]

Objectives: The antitumor effects of pyropheophorbide-α methyl ester-mediated photodynamic therapy (MPPa-PDT) were observed in several cancers. The objective of this investigation was to examine the antineoplastic efficacy of MPPa-PDT acting on lung carcinoma A549 cells and further elaborate mechanisms. Methods: The viability of A549 cells was examined with cell counting kit-8 after MPPa-PDT disposal. Hoechst 33342 staining, monodansylcadaverine (MDC) staining, and transmission electron microscopy were employed to observe apoptotic bodies and autophagic vesicles. Flow cytometry with Annexin V/propidium iodide (PI) labeling objectively assessed cell death. The expression of associated proteins, including Caspase-3, Beclin-1, LC-3II, and mitogen-activated protein kinase (MAPK) families concluding c-jun NH2-terminal kinase (JNK), p38 MAPK, and extracellular signal-regulated kinase 1/2 (ERK) were identified by Western blotting. Results: Prolonged exposure to MPPa-PDT gradually decreased lung cancer A549 cell viability. Apoptosis and autophagy activity were higher in the MPPa-PDT cohort in comparison to the control group. Meanwhile, autophagy inhibition enhanced cell-killing efficacy apparently. Besides, the JNK and p38 MAPK pathways were implicated in MPPa-PDT-triggered apoptosis and autophagy. Conclusions: This study demonstrated that JNK and p38 MAPK were engaged in MPPa-PDT-mediated apoptosis and autophagy in lung carcinoma A549 cells. [ABSTRACT FROM AUTHOR]

While surgical resection is a mainstay of cancer treatment, many tumors are unresectable due to stage, location, or comorbidities. Ablative therapies, which cause local destruction of tumors, are effective alternatives to surgical excision in several settings. Ethanol ablation is one such ablative treatment modality in which ethanol is directly injected into tumor nodules. Ethanol, however, tends to leak out of the tumor and into adjacent tissue structures, and its biodistribution is difficult to monitor in vivo. To address these challenges, this study presents a cutting‐edge technology known as Light‐Activatable Sustained‐Exposure Ethanol Injection Technology (LASEIT). LASEIT comprises a three‐part formulation: (1) ethanol, (2) benzoporphyrin derivative, which enables fluorescence‐based tracking of drug distribution and the potential application of photodynamic therapy, and (3) ethyl cellulose, which forms a gel upon injection into tissue to facilitate drug retention. In vitro drug release studies showed that ethyl cellulose slowed the rate of release in LASEIT by 7×. Injections in liver tissues demonstrated a 6× improvement in volume distribution when using LASEIT compared to controls. In vivo experiments in a mouse pancreatic cancer xenograft model showed LASEIT exhibited significantly stronger average radiant efficiency than controls and persisted in tumors for up to 7 days compared to controls, which only persisted for less than 24 h. In summary, this study introduced LASEIT as a novel technology that enabled real‐time fluorescence monitoring of drug distribution both ex vivo and in vivo. Further research exploring the efficacy of LASEIT is strongly warranted. [ABSTRACT FROM AUTHOR]

Introduction: Photodynamic Therapy (PDT) presents a non invasive avenue for treating various infections, including periodontal disease, offering an alternative to mechanical methods like scaling and root planing. Concerns about antibiotic resistance have fueled the exploration of PDT as an antimicrobial therapy. PDT combines low-power lasers with photosensitising drugs to eliminate microorganisms through the generation of cytotoxic reactive oxygen species upon light activation. Aim: To evaluate the scope of PDT and its role in periodontology. Materials and Methods: A comprehensive electronic search was conducted in major medical databases, including Google Scholar, PubMed, Cochrane Library, Scopus, Web of Science, Embase, and Wiley. A total of 43 studies from 2007 to 2023 were selected, focusing on PDT for the treatment of periodontal disease. The review included Randomised Controlled Trials (RCTs), case-control studies, and cohort studies involving human subjects, using Photosensitisers (PSs) or Indocyanine Green (ICG) for subgingival irrigation in chronic periodontitis patients after scaling and root planing, with follow-ups extending over one month. The outcomes measured were Probing Pocket Depth (PPD), Clinical Attachment Level (CAL), Plaque Index (PI), and Gingival Index (GI). Results: In present review, after thorough analysis, a total of 21 studies were selected from databases including Google Scholar, PubMed, Cochrane Library, Scopus, Web of Science, Embase, and Wiley. The risk of bias assessment showed high-risk in 1 out of 128 studies (0.59%), low risk in 139 out of 168 studies (82.74%), and unclear risk in 28 out of 168 studies (16.67%). The results indicated significant clinical improvements when PDT was combined with conventional treatments. Conclusion: The PDT in periodontology showcases varied roles, from antimicrobial action to tissue healing and the promotion of periodontal health. Its efficacy as an adjunctive treatment, especially in challenging cases or against resistant microbes, is evident, accentuated by its non invasive nature and minimal adverse effects, making it an appealing option in periodontal care. [ABSTRACT FROM AUTHOR]

Two‐photon photodynamic therapy (TP‐PDT), which utilizes near‐infrared light to excite photosensitizer via two‐photon excitation (TPE), is a promising modality in the treatment of deeply seated tumors or thick tumors. However, the TPE domain is much smaller than the tumor volume, significantly limiting the therapeutical outcomes of TP‐PDT. Here, a light‐sheet TPE system is designed and constructed using a cylindrical lens for highly efficient TP‐PDT. The light‐sheet TPE performance is characterized and optimized via theoretical analysis and experimental studies in solution, phantom, and tumor. The optimized excitation system can reach a large TPE domain of 2.6 × 2.7 × 0.09 mm in the tumor, which is not achievable using conventional TPE methods, enabling TPE and subsequently generated reactive oxygen species to cover the whole tumor under line‐scanning. Outstanding TP‐PDT therapeutic performance of 70% tumor growth inhibition rate is achieved under line‐scanned light‐sheet TPE, making the proposed light‐sheet excited TP‐PDT a potential therapeutic tool for future translational research. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) has been emerged as a promising modality for cancer treatment. However, the development of drug delivery system enabling continuous release of photosensitizers (PSs) for long-term PDT treatment still remains challenges. Herein, a H2O2-responsive injectable hydrogel, covalently crosslinked by N1-(4-boronobenzyl)-N3-(4-boronophenyl)-N1,N1,N3,N3-tetramethylpropane-1,3-diaminium (TSPBA) with PVA containing polythiophene quaternary ammonium salt (PT2) polymer dots (PDots) as a photosensitizer was fabricated. Under the stimulation of H2O2, the obtained injectable hydrogel gradually degrades and releases PDots. In vitro experiments suggested that the released PDots could realize efficient tumor cells inhibition through its robust singlet oxygen generation capability upon 577 nm laser irradiation. In vivo studies demonstrated a sustained retention of PDots for at least 7 days following single-dose administration, facilitating efficient tumor inhibition with light treatments for 3 times without apparent biotoxicity. This work presents an innovative polymer dots-based composite local drug delivery system for long-term PDT in cancer treatment. [ABSTRACT FROM AUTHOR]

Antimicrobial photodynamic inactivation (aPDI) offers a promising alternative to combat drug-resistant bacteria. This study explores the potential of lapachol, a natural naphthoquinone derived from Tabebuia avellanedae, as a photosensitizer (PS) for aPDI. Lapachol's photosensitizing properties were evaluated using Staphylococcus aureus and Escherichia coli strains under blue LED light (450 nm). UV-vis spectroscopy confirmed lapachol's absorption peak at 482 nm, aligning with effective excitation wavelengths for phototherapy. Photoinactivation assays demonstrated significant bacterial growth inhibition, achieving complete eradication of S. aureus at 25 µg·mL−1 under light exposure. Scanning electron microscopy (SEM) revealed morphological damage in irradiated bacterial cells, confirming lapachol's bactericidal effect. This research underscores lapachol's potential as a novel photosensitizer in antimicrobial photodynamic therapy, addressing a critical need in combating antibiotic resistance. [ABSTRACT FROM AUTHOR]

Guanine-quadruplex (G4) selective photosensitizers have huge potential for photodynamic therapy against various diseases correlated with G4 DNA and G4 RNAs; however, the types of photosensitizer skeletons available are limited. Herein, we investigated the ability of our original G4 ligands, tripodal quinone-cyanine dyes (tpQCy(s)), which were developed as fluorescent probes for G4, to act as photosensitizers for cancer-selective apoptosis inducers. The results indicated that the tpQCy skeleton has great potential for developing G4-targeted cancer-selective photosensitizers for photodynamic therapy. Among the two tpQCys, only QCy(BnBT)3, which has greater G4 selectivity, exhibited photoinduced cytotoxicity in HeLa cell growth, suggesting that the direct oxidation of G4 DNA or RNA is crucial for photoinduced cytotoxicity. RNA-seq analysis using a next-generation sequencing technique revealed that apoptosis was clearly induced by photoirradiation after QCy(BnBT)3 treatment. [ABSTRACT FROM AUTHOR]

The application of nanomaterials in tumor therapy is increasingly widespread, offering more possibilities for enhanced tumor therapy. However, the unclear biological distribution and metabolism of nanomaterials may lead to immune rejection or inflammatory reactions, posing numerous challenges to their clinical translation. The rich diversity and multifaceted functions of blood cells offer promising biological avenues for enhancing the application of nanoparticles in cancer therapy. Blood cell membranes, being made of naturally found components in the body, exhibit significant biocompatibility, which can reduce the body's immune rejection response, extend the drug's residence time in the bloodstream, and enhance its bioavailability. Integrating blood cell membranes with nanomaterials enhances tumor therapy by improving targeted delivery, prolonging circulation time, and evading immune responses. This review summarizes recent advancements in the application of blood cell membrane-coated nanomaterials for antitumor therapy, with a particular focus on their use in photodynamic and photothermal treatments. Additionally, it explores their potential for synergistic effects when combined with other therapeutic modalities. [ABSTRACT FROM AUTHOR]

Simple Summary: The International Agency for Research on Cancer (IARC) projects that by 2040, the global incidence of cancer would reach 27.5 million new cases. The current primary modalities of cancer treatment encompass surgery, radiation, and chemotherapy, which can harm normal tissues or fail to fully eliminate cancer. Nanomaterials make it easier to keep an eye on surgeries that remove tumors, deliver chemotherapy directly and selectively to cancer cells and neoplasms, and make radiation therapy more effective. It mitigates the risk and enhances the survival of cancer patients. This review aims to consolidate various metal peroxide nanomaterials utilized in cancer treatment with a special emphasis on metal peroxide nanoparticle surface modification for enhancing the efficacy of nanomaterials in tumor microenvironment. Researchers can acquire knowledge regarding metal peroxide nanoparticle types, their mechanisms of action, and their contributions to existing cancer medicines for enhanced cancer management. Background: The significant expansion of nanobiotechnology and nanomedicine has led to the development of innovative and effective techniques to combat various pathogens, demonstrating promising results with fewer adverse effects. Metal peroxide nanoparticles stand out among the crucial yet often overlooked types of nanomaterials, including metals. These nanoparticles are key in producing oxygen (O2) and hydrogen peroxide (H2O2) through simple chemical reactions, which are vital in treating various diseases. These compounds play a crucial role in boosting the effectiveness of different treatment methods and also possess unique properties due to the addition of metal ions. Methods: This review discusses and analyzes some of the most common metal peroxide nanoparticles, including copper peroxide (CuO2), calcium peroxide (CaO2), magnesium peroxide (MgO2), zinc peroxide (ZnO2), barium peroxide (BaO2), and titanium peroxide (TiOx) nanosystems. These nanosystems, characterized by their greater potential and treatment efficiency, are primarily needed in nanomedicine to combat various harmful pathogens. Researchers have extensively studied the effects of these peroxides in various treatments, such as catalytic nanotherapeutics, photodynamic therapy, radiation therapy, and some combination therapies. The tumor microenvironment (TME) is particularly unique, making the impact of nanomedicine less effective or even null. The presence of high levels of reactive oxygen species (ROS), hypoxia, low pH, and high glutathione levels makes them competitive against nanomedicine. Controlling the TME is a promising approach to combating cancer. Results: Metal peroxides with low biodegradability, toxicity, and side effects could reduce their effectiveness in treating the TME. It is important to consider the distribution of metal peroxides to effectively target cancer cells while avoiding harm to nearby normal cells. As a result, modifying the surface of metal peroxides is a key strategy to enhance their delivery to the TME, thereby improving their therapeutic benefits. Conclusions: This review discussed the various aspects of the TME and the importance of modifying the surface of metal peroxides to enhance their therapeutic advantages against cancer, as well as address safety concerns. Additionally, this review covered the current challenges in translating basic research findings into clinical applications of therapies based on metal peroxide nanoparticles. [ABSTRACT FROM AUTHOR]

Nanoparticles particularly titanium dioxide (TiO2) have demonstrated remarkable potential in both photocatalytic degradation of the toxic compounds and development of the effective photodynamic therapy (PDT) by harnessing light-induced reactive oxygen species (ROS) generation. In PDT, the choice of appropriate photosensitizers (PSs) and optimal light sources is crucial for the therapeutic efficacy. Pure titanium dioxide has the drawbacks of limited tissue penetration and high cytotoxicity due to the triggered traditional ultraviolet light sources, rapid recombination rate of the electron (e−)/hole (h+) pairs attributed to their broader band gap energy, and low solubility with high tendency to aggregation in water. Reproducible synthesis and efficiency optimization in ROS generation are also among the challenges. Addressing these challenges, this study focuses on the construction of a novel PDT nanoplatform: design and synthesis of the biocompatible N-doped-TiO2/FeTCPP (PFNT) by modifying TiO2 nanoparticles with urea as a safe nitrogen source (NT) to create an efficient type I PS, which expands the optical absorption capacity between 400 and 800 nm due to the facilitated localized nitrogen states within the titanium dioxide band gap, as well as by incorporating iron metalloporphyrin FeTCPP (tetra(4-carboxyphenyl) porphyrin) as an effective type II PS. Upon visible-light irradiation, FeTCPP not only sensitizes singlet oxygen, but also transfers electrons from excited FeTCPP* species to Ti4+-based N-TiO2 to afford FeTCPP•+ ligands and Ti3+ centers, thus propagating the production of hydrogen peroxide, superoxide, and hydroxyl radicals. By generating the substantial distinct ROS, significant tumor cell killing was obtained under LED irradiation, particularly in addressing melanoma. This research underscores substantial promise of the designed N‐TiO2/FeTCPP nanocomposites in advancing the field of PDT-based cancer therapy, paving the way for efficient and targeted treatments. [ABSTRACT FROM AUTHOR]

DNA origami nanostructures are promising carries for drug delivery applications. However, their limited stability under relevant conditions often presents a challenge. Herein, the structural stability of DNA origami nanostructures is investigated in a setting compatible with their application in photodynamic therapy (PDT). To this end, DNA origami triangles and six‐helix bundles (6HBs) are loaded with the clinically tested photosensitizer methylene blue, which upon irradiation with red light generates reactive oxygen species (ROS) that attack the DNA origami nanostructures. ROS‐induced structural damage is observed to depend on the ionic composition of the surrounding medium and becomes more severe at low ionic strength. Mg2+ ions can efficiently protect the DNA origami nanostructures from ROS‐induced damage and may even heal some of the damage obtained under Mg2+‐free conditions when added after irradiation. Finally, the employed DNA origami 6HBs are more resistant toward ROS‐induced structural damage than the triangles, which is attributed to their markedly different mechanical properties. These results thus provide some fundamental insights into the stabilizing role of DNA origami superstructure that may guide the selection or design of DNA origami nanocarriers with optimized stability for their application in PDT. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is an alternative to cancer treatment, demonstrating selectivity and significant cytotoxicity on malignant tissues. Such therapy involves two nontoxic components: photosensitizer (PS) and non-ionizing radiation. In optimal dosage combinations, PDT causes cellular and tissue effects by oxygen-dependent processes, leading tumor cells to regulated cell death pathways. Regulated necrosis, called necroptosis, can be triggered by PDT and is characterized by caspase-8 inhibition and RIPK1, RIPK3, and MLKL activities, leading to plasma membrane pores formation with subsequent cellular content release into the extracellular space. For this review, studies accessed by PubMed describing the relation between necroptosis and PDT were summarized. The results showed that PDT can trigger necroptosis mechanisms in different tumor cells. Moreover, a mix of different cell death types can co-occur. It is also important to highlight that necroptosis triggered by PDT is related to damage-associated molecular patterns (DAMPs) release, involving immunogenic cell death and vaccination. The cell death response is directly related to the photosensitizer chemical characteristics, concentration, incubation time, cellular location, and irradiation parameters. The synergism among all cell death types is an excellent advantage for avowing tumor resistance mechanisms and developing new solutions. [ABSTRACT FROM AUTHOR]

Organic photosensitizers (PSs) can generate reactive oxygen species (ROS) via electron transfer (type I) and energy transfer (type II) pathways during photodynamic therapy (PDT). However, although numerous organic PSs have been constructed, the methods to optimize both type I and type II ROS generation are still not well explored. In this work, molecular engineering is applied to design three new organic PSs with varying triplet lifetimes and intersystem crossing (ISC) efficiency to achieve highly efficient type I&II ROS generation. The results reveal that after coated into nanoparticles (NPs) with DSPE‐PEG2000‐Biotin, the PS of mBDP‐PyH with the longest triplet lifetime and moderate ISC efficiency possesses good type II ROS and moderate type I ROS generation. With other properties being similar, the PS of mBDP‐2Py exhibits a shorter triplet lifetime, accompanied by concurrently reduced ROS generation for both types inside NPs. In contrast, the most potent PS of mBDP‐PyBr exhibits the shortest triplet lifetime but highly efficient ISC, with its NPs showing superior type I&II ROS generation. Moreover, both in vitro and in vivo experiments indicate that mBDP‐PyBr NPs display outstanding light toxicity under normoxic and hypoxic conditions. Overall, this study provides valuable guidance in designing effective organic PSs for PDT. [ABSTRACT FROM AUTHOR]

Carbon nanomaterials, such as carbon quantum dots (CQDs), are excellent candidates for antibacterial agent development as they are cost-effective. Nitrogen-doped CQDs (N-doped CQDs) exhibit antibacterial activity against gram-positive bacteria. However, investigation of N-CQDs and their efficacy against the selected bacterial strains under visible light irradiation has not been carried out. Here, we aimed to evaluate N-CQDs for their efficacy as a photosensitizer for antimicrobial photodynamic therapy (aPDT). N-CQDs were synthesized using the hydrothermal method with 1,3,6-trinitropyrene (TNP) as the nitrogen and carbon source. Antimicrobial tests of N-CQDs were conducted against gram-positive (Bacillus subtilis NCIB 3610, Staphylococcus aureus Newman, and S. aureus USA300) and gram-negative (Escherichia coli K12) bacteria at different concentrations (0–100 mg/L). The N-CQDs exerted a moderate growth-inhibitory effect on gram-positive bacteria in the dark. However, in the presence of white light generated using 20-W light-emitting diode, N-CQDs could completely kill the bacteria at a low concentration of 20 mg/L. The minimal inhibitory concentration of N-CQDs for the two S. aureus strains (Newman and USA300) was 20 mg/L under light conditions, whereas that for B. subtilis was 100 mg/L. The results demonstrate that N-CQDs may be used as a photosensitizer in aPDT and as an antibacterial agent. [Display omitted] • Nitrogen-doped carbon quantum dots (N-CQDs) were produced by the hydrothermal method. • N-CQDs exerted moderate growth-inhibitory effect on gram-positive bacteria in dark. • Incubation with N-CQDs under the white light could completely kill the bacteria. • N-CQDs may be used as an antibacterial agent in antibacterial photodynamic therapy. [ABSTRACT FROM AUTHOR]

• This review can better inform discussions with HR-HPV+ women and answer their questions about alternatives to surveillance. • This paper is the first of its kind to compile treatment options for women with HPV persistence and low-grade changes only. • Meta-analysis showed some therapies may lead to earlier HR-HPV resolution and CIN regression compared with natural clearance. In 2021, the World Health Organisation (WHO) updated its guidelines for cervical screening from cytology testing to primary high-risk human papillomavirus (HR-HPV) testing. This change in testing has effectively led to a 'new disease' as women are now aware of having a virus that induces changes that can cause cancer, which they would have been unaware of previously. While current management involves a 'watch and wait' approach and no active treatment, the anxiety associated with having HR-HPV may prompt some women to seek 'treatments' outside the screening programme. ● to identify potential treatment options available for women with persistent HR-HPV and/or low-grade cervical intraepithelial neoplasia (CIN), i.e. ≤CIN 1. ● to determine the clinical effectiveness of these treatments, namely by: ◦ HR-HPV clearance rate, and/or: ◦ CIN regression. We searched MEDLINE, PubMed, EMBASE, Web of Science and the Cochrane Library. We included cohort studies and randomised controlled trials (RCTs) only. Records (n = 2135) were screened in Rayyan by two independent reviewers. Quality assessment was conducted using the ROBINS-I tool and the ROB-2 tool. 12 studies (four cohort studies and eight RCTs) were included: six oral medications, two topical medications, one vaccination, and three non-surgical device treatments. Meta-analysis revealed that some therapeutic interventions, including vaginal gels, photodynamic therapy, and some oral medications, may lead to earlier resolution of persistent HR-HPV and regression of low-grade CIN when compared with natural clearance. This review can better inform discussions with HR-HPV+ women and answer their questions about alternatives to surveillance. [ABSTRACT FROM AUTHOR]

High Epidermal growth factor receptor (EGFR) in Cutaneous Squamous Cell Carcinoma (cSCC) is associated with poor prognosis and advanced metastatic stages, severely impeding the efficacy of EGFR-targeting immunotherapy. This is commonly attributed to the combinatory outcomes of hypoxic tumor microenvironment (TME) and immunosuppressive effector cells together. Herein, a novel paradigm of EGFR-targeting oxygen-saturated nanophotosensitizers, designated as CHPFN-O 2 , has been specifically tailored to mitigate tumor hypoxia in EGFR-positive cSCC and achieve Cetuximab (CTX) - mediated immunotherapy (CIT). The conjugated CTX in CHPFN-O 2 serves to initiate immune responses by recruiting Fc receptor (FcR)-expressing immune effector cells towards tumor cells, thereby eliciting antibody-dependent cellular phagocytosis (ADCP), antibody-dependent cellular trogocytosis (ADCT) and antibody-dependent cellular cytotoxicity (ADCC). Besides, CHPFN-O 2 can engender a shift from a tumor-friendly to a tumor-hostile one through improved tumor oxygenation, contributing to oxygen-elevated photodynamic therapy (oxPDT). Notably, the combination of oxPDT and CIT eventually promotes T-cell-mediated antitumor activity and successfully inhibits the growth of EGFR-expressing cSCC with good safety profiles. This comprehensive oxPDT/CIT integration aims not only to enhance therapeutic efficacy against EGFRhigh cSCC but also to extend its applicability to other EGFRhigh malignancies, thus delineating a new avenue for the highly efficient synergistic treatment of EGFR-expressing malignancies. EGFR-targeting oxygen-saturated nanophotosensitizers are meticulously designed to improve tumor selectivity, alleviate tumor hypoxia, reverse tumor immunosuppression, and recruit immune effector cells, thus resulting in the synergy of Cetuximab-based immunotherapy (CIT) and oxygen-elevated photodynamic therapy (oxPDT) for remarkably enhancing T cell-mediated antitumor efficacy against EGFR-expressing cSCC with great clinical value. [Display omitted] • CHPFN-O 2 demonstrates promising antitumor activity and high biosafety. • CHPFN-O 2 alleviates tumor hypoxia and initiates CIT-mediated immune responses. • CHPFN-O 2 presenting a new treatment paradigm of synergistic oxPDT/CIT. • CHPFN-O 2 improves the tumor microenvironment of EGFR-expressing cSCC. • The clinical prospects of CHPFN-O 2 can be extended to other forms of cSCC. [ABSTRACT FROM AUTHOR]

An imine-based nanoscale COF has been synthesized and functionalized with a pyridone-derived structure to create a singlet oxygen-storing nanoplatform, which can continuously produce and release singlet oxygen to realize "afterglow" photodynamic therapy. [Display omitted] Photodynamic therapy (PDT) is an emerging treatment but often restricted by the availability of oxygen. Enhancing the lifespan of singlet oxygen (1O 2) by fractionated generation is an effective approach to improve the efficacy of PDT. Herein, an imine-based nanoscale COF (TpDa-COF) has been synthesized and functionalized with a pyridone-derived structure (Py) to create a 1O 2 -storing nanoplatform TpDa-COF@Py, which can reversibly capture and release 1O 2. Under 660 nm laser exposure, Py interacts with 1O 2 produced by the porphyrin motif in COF backbones to generate 1O 2 -enriched COF (TpDa-COF@Py + hv), followed by the release of 1O 2 through retro -Diels-Alder reactions at physiological temperatures. The continuous producing and releasing of 1O 2 upon laser exposure leads to an "afterglow" effect and a prolonged 1O 2 lifespan. In vitro cytotoxicity assays demonstrates that TpDa-COF@Py + hv exhibits an extremely low half-maximal inhibitory concentration (IC 50) of 0.54 µg/mL on 4T1 cells. Remarkably, the Py-mediated TpDa-COF@Py nanoplatform demonstrates enhanced cell-killing capability under laser exposure, attributed to the sustained 1O 2 cycling, compared to TpDa-COF alone. Further in vivo assessment highlights the potential of TpDa-COF@Py + hv as a promising strategy to enhance phototheronostics and achieve effective tumor regression. Accordingly, the study supplies a generalized 1O 2 "afterglow" nanoplatform to improve the effectiveness of PDT. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) and ferroptosis therapy have received extensive attention in breast cancer treatment. PDT induced apoptosis of tumor cells by producing a large amount of reactive oxygen species (ROS) under laser irradiation. Differently, ferroptosis therapy exerts its antitumor effect by inducing excessive accumulation of lipid peroxides on tumor cell membranes. Based on that, ROS produced by PDT may promote ferroptosis in tumor cells, and ferroptosis therapy is expected eliminate apoptosis-resistant tumor cells. Therefore, a synergistic ferroptosis-photodynamic therapy will be more effective and more potential in breast cancer treatment. Considering PDT has the characteristic of producing ROS, and neutrophil has a natural tendency to ROS, a neutrophil-mimetic hybrid liposome (CR-NML) was designed for co-delivery of the photosensitizer Ce6 and the ferroptosis inducer RSL3. CR-NML targeted tumor through the ROS tendency of neutrophil and the enhanced permeability and retention (EPR) effect of liposome, then induced both apoptosis and ferroptosis in tumor cells, which increased ROS level and finally realized ROS cascade amplification. The synergistic ferroptosis-photodynamic therapy demonstrated significant therapeutic efficacy in 4T1 tumor bearing mice, which provided a promising strategy for breast cancer treatment. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic skin disease characterized by the hyperproliferation of keratinocytes and an overactive autoimmune response. Photodynamic therapy (PDT) has been established as a promising intervention for alleviating psoriasis. However, the current transdermal delivery of photosensitizers is inefficient and imprecise. In this study, we developed a foamed microemulsion nanodroplets system containing chlorin e6 (Ce6 FM), exhibiting precise epidermal targeting and retention, which targeted the aberrantly proliferating epidermal cells at psoriatic skin lesions and avoided the damage to the normal cutaneous cells. Upon application in a psoriatic mouse model, Ce6 FM efficiently induced keratinocyte apoptosis by generating reactive oxygen species under laser. Furthermore, Ce6 FM-based PDT activated the cyclooxygenase-2-induced immunosuppressive pathway in keratinocytes, resulting in the amelioration of the autoimmune microenvironment in psoriatic skin. Additionally, Ce6 FM-based PDT did not induce skin damage or atrophy associated with non-targeted halometasone treatment. Overall, Ce6 FM-based PDT holds promise as an effective, safe and compliant strategy for psoriasis treatment. [ABSTRACT FROM AUTHOR]

Bioimaging is a well-known process for visualizing biological substances or biological pathways in the human body at a molecular level without any intrusion. It has been used in various domains biological of chemistry, drug discovery, and disease detection, due to its potential application attributes of high resolution, high sensitivity, high selectivity, and low cost. In recent years, the transition metal-based luminescent probes or photosensitizers have a distinctive feature in optical bioimaging and photodynamic therapy, in in vivo and in vitro, as compared to other types of probes and have a strong influence on discovering biological analytes. Photodynamic therapy, a non-systemic treatment, has attracted significant attention for its ability to localize the disease. This depends on the nature of the photosensitizers, light, and reactive oxygen species (ROS), produced through electron transport or energy transfer pathways. In PDT, a photosensitizer (PS) gets activated on exposure to light of a specific wavelength and provides energy to molecular oxygen on the tissue surfaces. This generates reactive oxygen species such as superoxide, singlet oxygen, and hydroxyl radicals causing damage to cellular membranes, lipids, proteins, and DNA. Further, it also results in cell death via apoptosis and necrosis on targeted cancer cells. The current review provides a literature overview on bioimaging and PDT applications of reported ruthenium and platinum complexes acting as luminescent probes. The extensively studied ligands, in this context, are bipyridine, phenanthroline, porphyrin, BODIPY, and ferrocene. These complexes have been studied for their potential anticancer activity against different cancer cells in both light and dark conditions. In addition, these probes also possess excellent photophysical characteristics of intense emission, with significant Stokes shifts, extended lifetimes, controllable toxicity, and excellent photostability. [ABSTRACT FROM AUTHOR]