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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]

Objective: The present study aimed to evaluate the local effect of antimicrobial photodynamic therapy (aPDT) as adjunctive treatment for Grade C periodontitis in molars teeth. Method and materials: Thirty-eight molar teeth from 11 patients were included in this split-mouth randomized clinical trial. The teeth were randomly divided into two groups (n = 19 each) that were submitted to conventional scaling and root planing in addition to aPDT (test group) and to scaling and root planing in addition to aPDT simulation (control group). The following periodontal parameters were obtained prior to treatment (baseline) and at 3 months after the intervention: bleeding on probing, probing depth, gingival recession, clinical attachment level, and furcation level. A 5% significance level was adopted in the statistical analysis. Results: Both groups exhibited improvement in the clinical parameters (P < .001). However, the reductions in bleeding on probing and probing depth were greater in the test group (P < .001). There were no significant differences in the other clinical parameters between groups (P ≥ .130). Conclusions: Molar teeth treated with aPDT and scaling and root planing showed superior clinical improvement compared to those submitted only to scaling and root planing. aPDT may be used as adjunctive treatment for Grade C periodontitis affecting molar teeth since it seems to improve the clinical response to conventional debridement. [ABSTRACT FROM AUTHOR]

A long-wavelength triggered cationic iridium(III) complex, Ir5, and its corresponding nanoparticles with the ability to generate type I and type II reactive oxygen species have been synthesised. The complex targets mitochondria and achieves an excellent photodynamic therapy effect in hypoxic cancer cells. [ABSTRACT FROM AUTHOR]

The twist fusion of a benzothiophene group and the introduction of a 4-methyloxystyryl donor group to the BODIPY core resulted in large spin–orbit coupling values and smaller singlet–triplet energy gaps for the novel infrared absorbed photosensitizers named BSBDP. They show a high reactive oxygen species efficiency exceeding 69% and a fluorescence quantum yield of 23% and are successfully applied in imaging-guided photodynamic therapy in vitro and in vivo. [ABSTRACT FROM AUTHOR]

[Display omitted] The clinical translation of photosensitizers based on ruthenium(II) polypyridyl complexes (RPCs) in photodynamic therapy of cancer faces several challenges. To address these limitations, we conducted an investigation to assess the potential of a cubosome formulation stabilized in water against coalescence utilizing a polyphosphoester analog of Pluronic F127 as a stabilizer and loaded with newly synthesized RPC-based photosensitizer [Ru(dppn) 2 (bpy-morph)](PF 6) 2 (bpy-morph = 2,2′-bipyridine-4,4′-diylbis(morpholinomethanone)), PS-Ru. The photophysical characterization of PS-Ru revealed its robust capacity to induce the formation of singlet oxygen (1O 2). Furthermore, the physicochemical analysis of the PS-Ru-loaded cubosomes dispersion demonstrated that the encapsulation of the photosensitizer within the nanoparticles did not disrupt the three-dimensional arrangement of the lipid bilayer. The biological tests showed that PS-Ru-loaded cubosomes exhibited significant phototoxic activity when exposed to the light source, in stark contrast to empty cubosomes and to the same formulation without irradiation. This promising outcome suggests the potential of the formulation in overcoming the drawbacks associated with the clinical use of RPCs in photodynamic therapy for anticancer treatments. [ABSTRACT FROM AUTHOR]

[Display omitted] Nanomedicines that combine reactive oxygen species (ROS)-responsive polyprodrug and photodynamic therapy have shown great potential for improving treatment efficacy. However, the consumption of ROS by overexpressed glutathione in tumor cells is a major obstacle for achieving effective ROS amplification and prodrug activation. Herein, we report a polyprodrug-based nanoparticle that can realize ROS amplification and cascaded drug release. The nanoparticle can respond to the high level of hydrogen peroxide in tumor microenvironment, achieving self-destruction and release of quinone methide. The quinone methide depletes intracellular glutathione and thus decreases the antioxidant capacity of cancer cells. Under laser irradiation, a large amount of ROS will be generated to induce cell damage and prodrug activation. Therefore, the glutathione-depleting polyprodrug nanoparticles can efficiently inhibit tumor growth by enhanced photodynamic therapy and cascaded locoregional chemotherapy. [ABSTRACT FROM AUTHOR]

[Display omitted] Whilst the development of advanced organic dots with aggregation-induced emission characteristics (AIE-dots) is being intensively studied, their clinical translation in efficient biotherapeutic devices has yet to be tackled. This study explores the synergistic interplay of oligo(styryl)benzenes (OSBs), potent fluorogens with an increased emission in the aggregate state, and Indocyanine green (ICG) as dual Near Infrared (NIR)-visible fluorescent nanovesicles with efficient reactive oxygen species (ROS) generation capacity for cancer treatment using photodynamic therapy (PDT). The co-loading of OSBs and ICG in different nanovesicles has been thoroughly investigated. The nanovesicles' physicochemical properties were manipulated via molecular engineering by modifying the structural properties of the lipid bilayer and the number of oligo(ethyleneoxide) chains in the OSB structure. Diffusion Ordered Spectroscopy (DOSY) NMR and spectrofluorometric studies revealed key differences in the structure of the vesicles and the arrangement of the OSB and ICG in the bilayer. The in vitro assessment of these OSB-ICG nanovesicles revealed that the formulations can increase the temperature and generate ROS after photoirradiation, showing for the first time their potential as dual photothermal/photodynamic (PTT/PDT) agents in the treatment of prostate cancer. Our study provides an exciting opportunity to extend the range of applications of OSB derivates to potentiate the toxicity of phototherapy in prostate and other types of cancer. [ABSTRACT FROM AUTHOR]

ABSTRACT Photodynamic therapy (PDT) is a promising treatment for cancer. At present, the development of photosensitizers has become a hot spot for research at home and abroad. In this study, 20 porphyrin‐butylphenol compounds were synthesized, and the structures of the target compounds were analyzed by means of 1H NMR, IR, mass spectrometry, and other analytical methods. The quantum yield of the target compound as a photosensitizer for the production of singlet oxygen was determined by using a DPBF reactive oxygen probe (1,3‐diphenylisobenzofuran). The anticancer activity of the synthesized target compounds was studied using HepG2 cells and A549 cells. The results of the singlet oxygen experiments showed that the Zn metal chelated compound had better singlet oxygen production than the free‐base porphyrin. The cellular activity assays showed that the metal‐chelated compounds exhibited better in vitro antitumor activity. [ABSTRACT FROM AUTHOR]

Breast cancer therapy has significantly advanced by targeting the programmed cell death-ligand 1/programmed cell death-1 (PD-L1/PD-1) pathway. BMS-202 (a smallmolecule PD-L1 inhibitor) induces PD-L1 dimerization to block PD-1/PD-L1 interactions, allowing the T-cell-mediated immune response to kill tumor cells. However, immunotherapy alone has limited effects. Clinically approved photodynamic therapy (PDT) activates immunity and selectively targets malignant cells. However, PDT aggravates hypoxia, which may compromise its therapeutic efficacy and promote tumor metastasis. We designed a tumor-specific delivery nanoplatform of liposomes that encapsulate the hypoxia-sensitive antitumor drug tirapazamine (TPZ) and the small-molecule immunosuppressant BMS. New indocyanine green (IR820)-loaded polyethylenimine-folic acid (PEI-FA) was complexed with TPZ and BMS-loaded liposomes via electrostatic interactions to form lipid nanocomposites. This nanoplatform can be triggered by near-infrared irradiation to induce PDT, resulting in a hypoxic tumor environment and activation of the prodrug TPZ to achieve efficient chemotherapy. The in vitro and in vivo studies demonstrated excellent combined PDT, chemotherapy, and immunotherapy effects on the regression of distant tumors and lung metastases, providing a reference method for the preparation of targeted agents for treating breast cancer. [ABSTRACT FROM AUTHOR]

Abnormal cancer metabolism causes hypoxic and immunosuppressive tumor microenvironment (TME), which limits the antitumor efficacy of photodynamic therapy (PDT). Herein, we report a photosensitizing nanoscale metal–organic layer (MOL) with anchored 3‐bromopyruvate (BrP), BrP@MOL, as a metabolic reprogramming agent to enhance PDT and antitumor immunity. BrP@MOL inhibited mitochondrial respiration and glycolysis to oxygenate tumors and reduce lactate production. This metabolic reprogramming enhanced reactive oxygen species generation during PDT and reshaped the immunosuppressive TME to enhance antitumor immunity. BrP@MOL‐mediated PDT inhibited tumor growth by >90 % with 40 % of mice being tumor‐free, rejected tumor re‐challenge, and prevented lung metastasis. Further combination with immune checkpoint blockade potently regressed the tumors with >98 % tumor inhibition and 80 % of mice being tumor‐free. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) utilizes reactive oxygen species (ROS) for eradication of cancer cells. Its effectiveness is governed by the oxygen content, which is scarce in the hypoxic tumor microenvironment. We report herein two zinc(II) phthalocyanines substituted with two or four nitric oxide (NO)‐releasing moieties, namely ZnPc‐2NO and ZnPc‐4NO, which can suppress the mitochondrial respiration, thereby sparing more intracellular oxygen for PDT. Using HT29 human colorectal adenocarcinoma cells and A549 human lung carcinoma cells, we have demonstrated that both conjugates release NO upon interaction with the intracellular glutathione, which can reduce the cellular oxygen consumption rate and adenosine triphosphate generation and alter the mitochondrial membrane potential. They can also relieve the hypoxic status of cancer cells and decrease the expression of hypoxia‐inducible factor protein HIF‐1α. Upon light irradiation, both conjugates can generate ROS and induce cytotoxicity even under a hypoxic condition, overcoming the oxygen‐dependent nature of PDT. Interestingly, the photodynamic action of ZnPc‐2NO elicits the release of damage‐associated molecular patterns, inducing the maturation of dendritic cells and triggering an antitumor immune response. The immunogenic cell death caused by this oxygen‐economized PDT has been demonstrated through a series of in vitro and in vivo experiments. [ABSTRACT FROM AUTHOR]

Singlet oxygen production and its reactivity have significant implications in fields ranging from polymer science to photodynamic therapy. Extensive research has focused on the development of organic-based materials and heavy metal complexes, including Ru(II), Rh(III), Ir(III) and Pt(II). However, metal complexes containing Au(I) have been scarcely explored and warrant further investigation. This review provides a comprehensive analysis of reported compounds, classified based on the ligands coordinated to the gold(I) centre. Additionally, future directions in photosensitizer development and singlet oxygen applications are discussed. [ABSTRACT FROM AUTHOR]

Phototherapy is a promising antitumor modality, which consists of photothermal therapy (PTT) and photodynamic therapy (PDT). However, the efficacy of phototherapy is dramatically hampered by local hypoxia in tumors, overexpression of indoleamine 2,3-dioxygenase (IDO) and programmed cell death ligand-1 (PD-L1) on tumor cells. To address these issues, self-assembled multifunctional polymeric micelles (RIMNA) were developed to co-deliver photosensitizer indocyanine green (ICG), oxygenator MnO2, IDO inhibitor NLG919, and toll-like receptor 4 agonist monophosphoryl lipid A (MPLA). It is worth noting that RIMNA polymeric micelles had good stability, uniform morphology, superior biocompatibility, and intensified PTT/PDT effect. What's more, RIMNA-mediated IDO inhibition combined with programmed death receptor-1 (PD-1)/PD-L1 blockade considerably improved immunosuppression and promoted immune activation. RIMNA-based photoimmunotherapy synergized with PD-1 antibody could remarkably inhibit primary tumor proliferation, as well as stimulate the immunity to greatly suppress lung metastasis and distant tumor growth. This study offers an efficient method to reinforce the efficacy of phototherapy and alleviate immunosuppression, thereby bringing clinical benefits to cancer treatment. [ABSTRACT FROM AUTHOR]

The outcomes of DFT‐based calculations are here reported to assess the applicability of two synthesized polypyridyl Ru(II) complexes, bearing ethynyl nile red (NR) on a bpy ligand, and two analogues, bearing modified‐NR, in photodynamic therapy. The absorption spectra, together with the non‐radiative rate constants for the S1 – Tn intersystem crossing transitions, have been computed for this purpose. Calculations evidence that the structural modification on the chromophore destabilizes the HOMO of the complexes thus reducing the H‐L gap and, consequently, red shifting the maximum absorption wavelength within the therapeutic window, up to 620 nm. Moreover, the favored ISC process from the bright state involves the triplet state closest in energy, which is also characterized by the highest SOC value and by the involvement of the whole bpy ligand bearing the chromophore in delocalising the unpaired electrons. These outcomes show that the photophysical behavior of the complexes is dominated by the chromophore. [ABSTRACT FROM AUTHOR]

Broadband near-infrared (NIR) light sources cover unique optical wavelengths and are valuable in the fields of bioimaging and photodynamic therapy, night vision lighting and security monitoring. NIR phosphor converted light-emitting diode (NIR pc-LED) devices have attractive features such as tunable emission peak, low cost of production, compact in sizes and high luminous efficiency. However, heat accumulation during operation due to poor thermal conductivity of the organic resin used in packaging often causes serious reduction in luminous efficiency and accelerated degradation of the device. In present work, we developed a Cr3+-doped transparent CaF 2 -based oxy-fluoride glass-ceramic (GC) that showed a broadband emission of 700∼1400 nm under 470 nm excitation. The emission peaked at ∼880 nm, the full-width at half maximum was about ∼297 nm, and the photoluminescence quantum yield reached ∼31.19 %. The emission was derived from the electronic transition of Cr3+ ions from the 4T 2 (F) to 4A 2 (F). Through structural analysis and numerical simulation, we showed that during the heat treatment process, Cr3+ ions were enriched into the CaF 2 crystal phase and replaced the Ca2+ in the GC host with occupied the center position of the polyhedrons, which provided a weak crystal field and led to NIR emission. We built NIR pc-LED devices using optimized GC and commercial blue LED chips, and we demonstrated the application of this NIR pc-LED in night-vision lighting. Our approaches to prepare simple and stable inorganic NIR luminous materials sealed in bulk in a transparent CaF 2 -based oxy-fluoride GC and to construct pc-LED devices could provide new concept to the field and have practical implications to applications in related fields. [ABSTRACT FROM AUTHOR]

Nanozymes have obvious advantages in improving the efficiency of cancer treatment. However, due to the lack of tissue specificity, low catalytic efficiency, and so on, their clinical applications are limited. Herein, the nanoplatform CeO2@ICG@GOx@HA (CIGH) with self‐accelerated cascade reactions is constructed. The as‐prepared nanozyme shows the superior oxidase (OXD)‐like, superoxide dismutase (SOD)‐like, catalase (CAT)‐like and peroxidase (POD)‐like activities. At the same time, under 808 nm near‐infrared (NIR) irradiation, the photodynamic and photothermal capabilities are also significantly enhanced due to the presence of indocyanine green (ICG). We demonstrate that the nanozyme CIGH can efficiently accumulate in the tumor and exhibit amplified cascade antitumor effects with negligible systemic toxicity through the combination of photodynamic therapy (PDT), photothermal therapy (PTT), chemodynamic therapy (CDT) and starvation therapy. The nanozyme prepared in this study provides a promising candidate for catalytic nanomedicines for efficient tumor therapy. [ABSTRACT FROM AUTHOR]

In recent years, all over the world mortality rate has been increasing drastically owing to cancer. This global challenge has aroused the researchers to develop novel technology. Among that, Photodynamic therapy (PDT) is an advanced therapeutic modality that can be used as an alternate to chemotherapy, and radiotherapy. PDT is drawing much researcher consideration as targeted cell can be killed straight forwardly by the use of it without aggressive damage to the adjacent cell. However, its application is restricted due to inherent limitations of the conventional photosensitizers (PSs) like lacking of tumor targeting capability, inadequate light penetration, restricted PS accumulation etc. Interestingly, owing to inherent optical property and tuneable ability, uses of nanoparticles (NPs) in PDT show a grand assure to conquer the limitations. Therefore, recently nanomaterial‐based PSs, whose physicochemical properties offer multifunctional and multimodal nanoplatform for various applications such as bioimaging, bioanalytical, and therapeutic etc. is gaining much more attention. In the present review, the basic concept of photodynamic therapy, its principle and types are discussed. Subsequently, role of different organic and inorganic‐based nanomaterials in photodynamic therapy to cure cancer are highlighted. [ABSTRACT FROM AUTHOR]

This study investigated the potential use of curcumin‐mediated photodynamic treatment as a postharvest decontamination technique to reduce microbial load and growth and therefore extend the shelf life of strawberries. Curcumin was applied on strawberries, followed by illumination and storage at 4°C for 16 days. Strawberries were evaluated for decay, microbial load, and physicochemical properties such as weight loss, color, and firmness during storage. The findings revealed that curcumin‐mediated photodynamic treatment effectively reduced the decay incidence and severity in strawberries, with 20% less decay occurrence compared to untreated fruits, which was shown to be dependent on curcumin concentration. While a complete reduction in microbial load was observed upon treatment, microbial growth remained unaffected throughout storage. Moreover, photodynamic treatment did not show any adverse impact on color properties and firmness of strawberries. This eco‐friendly technique presents potential for fruit's shelf‐life extension, although optimization of treatment parameters and photodynamic unit design seems to be essential. [ABSTRACT FROM AUTHOR]

Objective: To assess the effectiveness of antimicrobial photodynamic therapy (aPDT) employing an annatto-based (20%) dye combined with blue LED for the treatment of halitosis in mouth-breathing children. Materials and methods: Fifty-two children six to twelve years of age with diagnoses of mouth breathing and halitosis (score of ≥ 3 on portable breath meter) Breath Alert™ (Tanita Corporation®-Japan), were randomly allocated to two groups (n = 26). Group 1: brushing, dental floss and aPDT applied to middle third of the dorsum of the tongue. Group 2: brushing, dental floss and tongue scraper. Breath meter results before, immediately after treatment as well as seven and 30 days after treatment were compared. The hypothesis of normality in the data was discarded by the Shapiro-Wilk test (p < 0.05) and for statistical analysis the Wilcoxon and Mann-Whitney tests were used. Results: A significant difference was found between the pre-treatment reading and all other readings (p < 0.05) in both groups, suggesting the effectiveness of the proposed treatments. No significant difference was found between the post-treatment reading and two follow-up readings, suggesting the maintenance of the effect of treatment over time (p > 0.05). However, significant differences were found between groups for all post-treatment assessments (p < 0.0001 for all comparisons), indicating greater effectiveness with aPDT. No association was found between the initial reading and the presence of coated tongue. Conclusion: Antimicrobial photodynamic therapy using annatto and blue LED proved to be a viable therapeutic option for the treatment of halitosis in mouth-breathing children. [ABSTRACT FROM AUTHOR]

By integrating TiO2 with rare earth upconversion nanocrystals (NaREF4), efficient energy transfer can be achieved between the two subunits under near‐infrared (NIR) excitation, which hold tremendous potential in the fields of photocatalysis, photodynamic therapy (PDT), etc. However, in the previous studies, the combination of TiO2 with NaREF4 is a non‐epitaxial random blending mode, resulting in a diminished energy transfer efficiency between the NaREF4 and TiO2. Herein, we present a fluorine doping‐mediated epitaxial growth strategy for the synthesis of TiO2‐NaREF4 heteronanocrystals (HNCs). Due to the epitaxial growth connection, NaREF4 can transfer energy through phonon‐assisted pathway to TiO2, which is more efficient than the traditional indirect secondary photon excitation. Additionally, F doping brings oxygen vacancies in the TiO2 subunit, which further introduces new impurity energy levels in the intrinsic band gap of TiO2 subunit, and facilitates the energy transfer through phonon‐assisted method from NaREF4 to TiO2. As a proof of concept, TiO2‐NaGdF4 : Yb,Tm@NaYF4@NaGdF4 : Nd@NaYF4 HNCs were rationally constructed. Taking advantage of the dual‐model up‐ and downconversion luminescence of the delicately designed multi‐shell structured NaREF4 subunit, highly efficient photo‐response capability of the F‐doped TiO2 subunit and the efficient phonon‐assisted energy transfer between them, the prepared HNCs provide a distinctive nanoplatform for bioimaging‐guided NIR‐triggered PDT. [ABSTRACT FROM AUTHOR]

Malignant melanoma (MM) is an extremely aggressive and fatal form of skin cancer that primarily affects the bottom layer of the epidermis and is associated with poor clinical outcomes. Early-stage MM is typically treated through surgical removal, while chemotherapy and radiotherapy are common conventional treatment options that come with harmful side effects. Emerging therapies such as immunotherapy, photodynamic therapy, biologic therapy, and photothermal therapy present hopeful options for treatment due to their effective and secure drug delivery methods. To address the limitations of current treatment options, advanced methods of drug delivery for subcutaneous MM are being developed, with hydrogels emerging as a promising alternative. To date, significant advancements have been made in the treatment of MM through the use of hydrogels-based drug delivery systems through focal plastering, injection, implantation, and microneedles. Recent research on hydrogel-based drug delivery systems that integrate multiple therapies for the treatment of subcutaneous MM is discussed in this review. [ABSTRACT FROM AUTHOR]

Phototherapy utilizing bacterial carriers has demonstrated efficacy in anti-tumor therapy, while the poor delivery of phototherapeutic agents and immunogenicity of microbial substances remain problematic. Herein, we develop a nanocoated bacterial delivery system (IF-S.T) that in situ forms the efficient photothermal agents via biomineralization and improves the intracellular oxygenation, thus triggering the self-enhanced photothermal therapy (PTT) and photodynamic therapy (PDT) on tumor. We densely coat self-assembled IF (ICG-Fe2+) nanocomplex onto the surface of LT2, weakly virulent strain of Salmonella typhimurium (S.T), by bioadaptive nanocoating techniques, masking bacterial virulence factors and reducing the potential immune adverse effects. Upon penetrating into the tumor environment, IF-S.T responds to H 2 O 2 to trigger the removal of the IF coating, where S.T produces excess hydrogen sulfide (H 2 S). H 2 S reacts with Fe2+, yielding ferrous sulfide (FeS) for PTT, and inhibits mitochondrial respiration to enhance tumor cell oxygenation for PDT. Consequently, IF-S.T plus laser irradiation exhibits direct tumor cells killing and elicits robust antitumor immune responses, leading to the complete tumor elimination. Thus, IF-S.T represents a promising platform for effective tumor delivery of photoactive agents for improved PTT/PDT efficacy. IF nanocomplex was coated onto bacteria (S.T) surface and detached in response to H 2 O 2. S.T produced H 2 S to react with Fe2+, in situ yielding FeS as an efficient photothermal agent. [Display omitted] • Utilizing bacteria metabolism to induce formation of photothermal agent in tumor. • H 2 O 2 -responsive nanocoating enables tumor-targeted biomineralization triggering. • Reducing the toxicity of bacteria by nanocoating based on self-assembly. [ABSTRACT FROM AUTHOR]

This study evaluates, in vitro, the effects of ozonated water as auxiliary endodontic irrigating and photodynamic therapy on the bond strength of fiberglass posts to root dentin. Sixty bovine incisors were prepared and divided into six groups (n=10):Oxidation only G1 Distilled water G2 5.25% NaOCl G3 10–15mg/L O3. Ox+PDT G4 DW+PDT G5 NaOCl+PDT G6 O3+PDT. Anatomical fiberglass posts were cemented and the roots were sectioned and submitted to the push-out test. Bond strength values were analyzed with two-way ANOVA and Tukey 5%. Failure patterns were analyzed. Sodium hypochlorite and ozonated water without photodynamic therapy showed the highest bond strength, and sodium hypochlorite with photodynamic therapy had the lowest bond strength. The O3+PDT association showed intermediate results. Considering that the main purpose of the O3 is disinfection, it was noted that ozonated water did not interfere on the bond strength of fiberglass posts to root dentin. Photodynamic therapy affected bond strength, mainly when associated with sodium hypochlorite. The ozonated water increases the PDT bond strength results. [ABSTRACT FROM AUTHOR]

The design, synthesis, and characterization of novel BODPY‐based iridium and ruthenium complexes were reported. The structures of new compounds were fully characterized by FT‐IR, MALDI‐TOF mass analysis, elemental analysis, 1H, and 19F NMR spectroscopies. Precursor BODIPY was characterized by single‐crystal x‐ray diffraction technique for the first time. Photophysical properties including absorption and emission profiles and lifetimes were investigated via UV–vis absorption and emission spectroscopy. Photochemical properties were investigated via direct method, and the singlet oxygen production capabilities of new complexes were determined by NIR phosphorescence methods. BODIPY‐based new complexes were efficient at producing 1O2. Besides, both complexes showed more remarkable photosensitization ability than some commonly used photosensitizer based on BODIPY derivatives. This study points out that novel complexes are effective 1O2 photosensitizers that might be used for different application areas like photodynamic therapy. [ABSTRACT FROM AUTHOR]

Conventional topical psoriasis treatments suffer from limited delivery to affected areas and skin irritation due to high local drug concentration. This study aims to prepare hypericin (HYP) loaded nanostructured lipid carriers (NLCs) and their application in psoriasis treatment through intradermal administration using hollow microneedles assisted by photodynamic therapy. The colloidal characteristics of NLCs, entrapment efficiency and morphology were evaluated. An ex-vivo skin distribution study was conducted along with testing the in vivo antipsoriatic activity in mice with the imiquimod-induced psoriasis model. The particle size and zeta potential of HYP-NLCs were 167.70 nm and −18.1, respectively. The ex-vivo skin distribution study demonstrated the superior distribution of HYP-NLCs to a depth of 1480 µm within the skin layers relative to only 750 µm for free HYP. In vivo studies revealed that the levels of NF-KB, IL 6, MMP1, GSH, and catalase in the group treated with HYP-NLCs in the presence of light were comparable to the negative control. The histopathological inspection of dissected skin samples reflected the superiority of HYP-NLCs over HYP ointment. This could be ascribed to the effect of nanoencapsulation on improving HYP properties besides the ability of hollow microneedles to ensure effective HYP delivery to the affected psoriatic area. [ABSTRACT FROM AUTHOR]

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

Breast cancer presents a significant global health challenge, ranking highest incidence rate among all types of cancers. Functionalised nanocarriers offer a promising solution for precise drug delivery by actively targeting cancer cells through specific receptors, notably folate receptors. By overcoming the limitations of passive targeting in conventional therapies, this approach holds the potential for enhanced treatment efficacy through combination therapy. Encouraging outcomes from studies like in vitro and in vivo, underscore the promise of this innovative approach. This review explores the therapeutic potential of FA (Folic acid) functionalised nanocarriers tailored for breast cancer management, discussing various chemical modification techniques for functionalization. It examines FA-conjugated nanocarriers containing chemotherapeutics to enhance treatment efficacy and addresses the pharmacokinetic aspect of these functionalised nanocarriers. Additionally, the review integrates active targeting via folic acid with theranostics, photothermal therapy, and photodynamic therapy, offering a comprehensive management strategy. Emphasising rigorous experimental validation for practical utility, the review underscores the need to bridge laboratory research to clinical application. While these functionalised nanocarriers show promise, their credibility and applicability in real-world settings necessitate thorough validation for effective clinical use. [ABSTRACT FROM AUTHOR]

Osteomyelitis, a grave deep tissue infection primarily caused by Staphylococcus aureus , results in serious complications such as abscesses and sepsis. With the incidence from open fractures exceeding 30 % and prevalent antibiotic resistance due to extensive treatment regimens, there's an urgent need for innovative, antibiotic-free strategies. Photothermal therapy (PTT) and photodynamic therapy (PDT) renowned for generating localized reactive oxygen species (ROS), face limitations in penetration depth. To overcome this, our method combines the deep penetration attributes of medical microwaves (MW) with the synergistic effects of the ZnO/ZrO 2 solid solution. Comprehensive in vitro and in vivo evaluations showcased the solid-solution's potent antibacterial efficacy and biocompatibility. The ZnO/ZrO 2 solid solution, especially in a 7:3 M ratio, manifests superior microstructural characteristics, optimizing MW-assisted therapy. Our findings highlight the potential of this integrated strategy as a promising avenue in osteomyelitis management. [Display omitted] • The ZnO/ZrO 2 (7:3) solid solution, showing largest surface area, good solid solution degree and more surface Ov. • The ZnO/ZrO 2 solid solution exhibited high bactericidal efficiency under MW-induced thermal and dynamic effects. • ZnO/ZrO 2 solid solution has commendable biocompatibility. [ABSTRACT FROM AUTHOR]

Using a photosensitizer (PS), light, and oxygen, photodynamic therapy creates cytotoxic reactive oxygen species, such as singlet oxygen (1O2), that kill cancer cells. Many cancer cell lines have up to 300 times more folic acid receptors than healthy cells. Therefore, folic acid is often used to improve selectivity of PSs. Photobleaching poses a disadvantage for PSs. In this paper, we have studied the photoinduced changes of meso-substituted cationic pyridyl porphyrins in the presence of folic acid using fluorescence and absorption spectroscopy. In this work, it was demonstrated that L-histidine, which is a 1O2 quencher, and D-mannitol, which is a hydroxyl radical quencher, can reduce photobleaching of cationic porphyrins and their interaction products with FA. This implies both singlet oxygen and hydroxyl radicals are involved in photobleaching. Additionally, our study revealed certain important features of the photobleaching of cationic porphyrins in the presence of folic acid. [ABSTRACT FROM AUTHOR]

The article provides a comprehensive overview of acne vulgaris, focusing on its pathophysiology and management strategies. Topics discussed include factors influencing acne such as androgen activity and genetic variants, the impact of lifestyle and dietary behaviors, and current treatment options ranging from topical and oral medications to isotretinoin.

Background: Phakomatosis pigmentovascularis (PPV) is a rare congenital syndrome. Only a few studies have reported the treatment of PPV, including a case using photodynamic therapy (PDT) to treat PPV‐associated port‐wine stains (PWS). Objective: To investigating the efficacy and adverse effects of hemoporfin‐PDT in PPV‐associated PWS. Methods: The efficacy and adverse effects in patients with PPV who underwent two sessions of hemoporfin‐PDT from January 2019 to December 2022 were retrospectively analyzed. Results: Twenty patients were included (13 females, 7 males, age range: 2–31 years; mean: 8.20 ± 8.92 years). Two, nine, seven, and two patients had PPV types Ia, IIa, IIb, and IIIa, respectively. After two treatments, the visual evaluation indicated the color of the PWS in 4, 5, 6, and 5 patients showed poor, fair, good, and excellent improvements, respectively. The combined good and excellent improvement rates in patients with PWS and pigmentary nevus overlapping in the same treatment area and in patients with PWS in the treatment areas only were 33.3% versus 87.5%, respectively, and were significantly different (p = 0.02). Minor side effects, such as edema, scabbing, hyperpigmentation, and blistering, were observed in some patients after PDT. Conclusion: Hemoporfin‐PDT is an effective treatment for PPV‐associated PWS. Patients with PWS and pigmentary nevus overlapping in the same treatment area showed poorer efficacy than patients with PWS in the treatment areas only. [ABSTRACT FROM AUTHOR]

The immunosuppressive phenotype of tumor cells extensively attenuates the immune activation effects of traditional treatments. In this work, a transferrin receptor (TfR) targeted immunostimulant (PTI) is fabricated for photodynamic immunotherapy against metastatic tumors by interrupting β -catenin signal pathway. To synthesize PTI, the photosensitizer conjugated TfR targeting peptide moiety (Palmitic-K(PpIX)-HAIYPRH) is unitized to encapsulate the transcription interrupter of ICG-001. On the one hand, the recognition of PTI and TfR can promote drug delivery into tumor cells to destruct primary tumors through photodynamic therapy and initiate an immunogenic cell death with the release of tumor-associated antigens. On the other hand, PTI will interrupt the binding between β -catenin and cAMP response element-binding protein (CREB), regulating the gene transcription to downregulate programmed death ligand 1 (PD-L1) while upregulating C–C motif chemokine ligand 4 (CCL4). Furthermore, the elevated CCL4 can recruit the dendritic cells to present tumor-specific antigens and promote T cells activation and infiltration, and the downregulated PD-L1 can avoid the immune evasion of tumor cells and activate systemic anti-tumor immunity to eradicate lung metastasis. This work may inspire the development of antibody antibody-free strategy to activate systemic immune response in consideration of immunosuppressive conditions. A transferrin receptor-targeted immunostimulant (PTI) is developed for photodynamic immunotherapy against metastatic tumors by downregulating programmed death ligand 1 (PD-L1) and upregulating C–C motif chemokine ligand 4 (CCL4). [Display omitted] [ABSTRACT FROM AUTHOR]

Ferroptosis is a recently discovered pathway for regulated cell death pathway. However, its efficacy is affected by limited iron content and intracellular ion homeostasis. Here, we designed a metal-organic framework (MOF)-based nanoplatform that incorporates calcium peroxide (CaO 2) and oridonin (ORI). This platform can improve the tumor microenvironment and disrupt intracellular iron homeostasis, thereby enhancing ferroptosis therapy. Fused cell membranes (FM) were used to modify nanoparticles (ORI@CaO 2 @Fe-TCPP, NPs) to produce FM@ORI@CaO 2 @Fe-TCPP (FM@NPs). The encapsulated ORI inhibited the HSPB1/PCBP1/IREB2 and FSP1/COQ10 pathways simultaneously, working in tandem with Fe3+ to induce ferroptosis. Photodynamic therapy (PDT) guided by porphyrin (TCPP) significantly enhanced ferroptosis through excessive accumulation of reactive oxygen species (ROS). This self-amplifying strategy promoted robust ferroptosis, which could work synergistically with FM-mediated immunotherapy. In vivo experiments showed that FM@NPs inhibited 91.57% of melanoma cells within six days, a rate 5.6 times higher than chemotherapy alone. FM@NPs were biodegraded and directly eliminated in the urine or faeces without substantial toxicity. Thus, this study demonstrated that combining immunotherapy with efficient ferroptosis induction through nanotechnology is a feasible and promising strategy for melanoma treatment. An iron-based metal-organic framework nanoplatform for enhanced ferroptosis therapy as a comprehensive antitumor strategy was reported. [Display omitted] [ABSTRACT FROM AUTHOR]

Crizotinib (CRZ), one of anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs), has emerged as a frontline treatment for ALK-positive (ALK+) lung adenocarcinoma. However, the overexpression of P-glycoprotein (P-gp, a mitochondrial adenosine triphosphate (ATP)-dependent protein) in lung adenocarcinoma lesions causes multidrug resistance (MDR) and limits the efficacy of CRZ treatment. Herein, a mitochondria-targeting nanosystem, zeolitic imidazolate framework-90@indocyanine green (ZIF-90@ICG), was fabricated to intervene in mitochondria and overcome drug resistance. Due to the zinc ion (Zn2+) interference of ZIF-90 and the photodynamic therapy (PDT) of ICG, this nanosystem is well suited for damaging mitochondrial functions, thus downregulating the intracellular ATP level and inhibiting P-gp expression. In addition, systematic bioinformatics analysis revealed the upregulation of CD44 in CRZ-resistant cells. Therefore, hyaluronic acid (HA, a critical target ligand of CD44) was further modified on the surface of ZIF-90@ICG for active targeting. Overall, this ZIF-90@ICG nanosystem synergistically increased the intracellular accumulation of CRZ and reversed CRZ resistance to enhance its anticancer effect, which provides guidance for nanomedicine design to accurately target tumours and induce mitochondrial damage and represents a viable regimen for improving the prognosis of patients with ALK-TKIs resistance. The original aim of our research was to combat multidrug resistance (MDR) in highly aggressive and lethal lymphoma kinase-positive (ALK+) lung adenocarcinoma. For this purpose, a cascade-targeted system was designed to overcome MDR, integrating lung adenocarcinoma-targeted hyaluronic acid (HA), mitochondrion-targeted zeolitic imidazolate framework-90 (ZIF-90), the clinically approved drug crizotinib (CRZ), and the fluorescence imaging agent/photosensitizer indocyanine green (ICG). Moreover, using a "two birds with one stone" strategy, ion interference and oxidative stress induced by ZIF-90 and photodynamic therapy (PDT), respectively, disrupt mitochondrial homeostasis, thus downregulating adenosine triphosphate (ATP) levels, inhibiting MDR-relevant P-glycoprotein (P-gp) expression and suppressing tumour metastasis. Overall, this research represents an attempt to implement the concept of MDR reversal and realize the trade-offs between MDR and therapeutic effectiveness. [Display omitted] [ABSTRACT FROM AUTHOR]

The effectiveness of tumor treatment using reactive oxygen species as the primary therapeutic medium is hindered by limitations of tumor microenvironment (TME), such as intrinsic hypoxia in photodynamic therapy (PDT) and overproduction of reducing glutathione (GSH) in chemodynamic therapy (CDT). Herein, we fabricate metal-polyphenol self-assembled nanodots (Fe@BDP NDs) guided by second near-infrared (NIR-II) fluorescence imaging. The Fe@BDP NDs are designed for synergistic combination of type-I PDT and CDT-amplified ferroptosis. In a mildly acidic TME, Fe@BDP NDs demonstrate great Fenton activity, leading to the generation of highly toxic hydroxyl radicals from overproduced hydrogen peroxide in tumor cells. Furthermore, Fe@BDP NDs show favorable efficacy in type-I PDT, even in tolerating tumor hypoxia, generating active superoxide anion upon exposure to 808 nm laser irradiation. The significant efficiency in reactive oxygen species (ROS) products results in the oxidation of sensitive polyunsaturated fatty acids, accelerating lethal lipid peroxidation (LPO) bioprocess. Additionally, Fe@BDP NDs illustrate an outstanding capability for GSH depletion, causing the inactivation of glutathione peroxidase 4 and further promoting lethal LPO. The synergistic type-I photodynamic and chemodynamic cytotoxicity effectively trigger irreversible ferroptosis by disrupting the intracellular redox homeostasis. Moreover, Fe@BDP NDs demonstrate charming NIR-II fluorescence imaging capability and effectively accumulated at the tumor site, visualizing the distribution of Fe@BDP NDs and the treatment process. The chemo/photo-dynamic-amplified ferroptotic efficacy of Fe@BDP NDs was evidenced both in vitro and in vivo. This study presents a compelling approach to intensify ferroptosis via visualized CDT and PDT. In this study, we detailed the fabrication of metal-polyphenol self-assembled nanodots (Fe@BDP NDs) guided by second near-infrared (NIR-II) fluorescence imaging, aiming to intensify ferroptosis via the synergistic combination of type-I PDT and CDT. In a mildly acidic TME, Fe@BDP NDs exhibited significant Fenton activity, resulting in the generation of highly toxic •OH from overproduced H 2 O 2 in tumor cells. Fe@BDP NDs possessed a remarkable capability for GSH depletion, resulting in the inactivation of glutathione peroxidase 4 (GPX4) and further accelerating lethal LPO. This study presented a compelling approach to intensify ferroptosis via visualized CDT and PDT. [Display omitted] [ABSTRACT FROM AUTHOR]

Extramammary Paget disease is a rare cutaneous malignancy that most commonly affects the genitals, perianal area, and axilla of elderly patients. Delays in care often lead to high levels of disease burden for patients. Thus, evidence-based recommendations are paramount in mitigating morbidity and mortality for this unique patient population. This 2-part continuing medical education series provides a complete picture of extramammary Paget disease. Part 2 of this continuing medical education series focuses on the complex management of extramammary Paget disease including surgical and noninvasive therapies, as well as novel approaches for advanced disease. [ABSTRACT FROM AUTHOR]

The reactive oxygen species (ROS) generation from photosensitizer in photodynamic therapy (PDT) is limited by tumor hypoxia. Even type-I photosensitizers, e.g., sulfur-substituted Nile blue, still rely on oxygen as the main center for transferring electrons to generate ROS. Cutting off the pathway of oxygen consumption in tumor can help photosensitizers overcome the limitation of low oxygen, in order to efficiently generate more ROS. It is known that glycolysis inhibitor 3-bromopyruvic acid (3-BP), which could specially target mitochondria, can provide more oxygen by inhibiting oxidative phosphorylation. Herein, we successfully designed and synthesized a new 3-BP-coupled sulfur-substituted Nile blue as prodrug (NBBP) for chemical/photodynamic synergistic therapy. Major results indicated that the protons in tumor catalyzed the hydrolysis of NBBP, inhibited photoinduced electron transfer between 3-BP and the photosensitizer in NBBP and further assisted the photosensitizer to be localized in mitochondria, utilizing local oxygen as much as possible and kill tumor cells more efficiently. Moreover, the glycolysis inhibition-induced autophagy was combined with PDT-induced autophagy, which could promote the deaths of tumor cells. Unlike other remedies exploiting nanomaterials, this construction method of NBBP achieves the efficient synergy of photodynamic therapy and glycolysis inhibition, stronger than their theoretical addition, in spatiotemporal dimensions. Our study provides not only a highly efficient platform for tumor therapy but also a design approach for prodrugs with synergistic effects. [ABSTRACT FROM AUTHOR]

It is desirable but always challenging to develop a cutting-edge tumor treatment strategy with high therapeutic efficacy, lesion-targeted precision and mild accessibility. Compared to traditional treatment modalities, photodynamic therapy has been widely studied since the generation of reactive oxygen species (ROS) at cancerous lesions unprecedentedly offers a convenient approach for localized tumor eliminations. Nevertheless, the consumption of oxygen for ROS production in a hypoxic tumor micro-environment has dramatically limited its feasibility and efficacy. Herein, the engineered nanocomposites of BTO@PDA-ICG-HA with photodynamic and pyroelectric performances have been fabricated and applied to the photodynamic-pyroelectric dynamic treatments. The continuing ROS production derived from intracellular oxygen (O2) and water (H2O) by laser irradiation contributed to the superb tumor cell apoptosis and significant tumor growth inhibition. Thus, this study has validated a new concept by depositing the engineered nanocomposites at the tumor just like Trojan horses, facilitating ROS release as killers and exerting the NIR-induced cell apoptosis and tumor growth inhibition with high therapeutic efficiency and expectable translational perspectives. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a promising cancer treatment. This study investigated the antitumor effects and mechanisms of a novel photosensitizer meso-5-[-diethylene triamine pentaacetic acid-aminophenyl]-10,15,20-triphenyl-porphyrin (DTP) mediated PDT (DTP-PDT). Cell viability, reactive oxygen species (ROS), and apoptosis were measured with a Cell Counting Kit-8 assay, DCFH-DA fluorescent probe, and Hoechst staining, respectively. Cell apoptosis- and autophagy-related proteins were examined using western blotting. RNA sequencing was used to screen differentially expressed mRNAs (DERs), and bioinformatic analysis was performed to identify the major biological events after DTP-PDT. Our results show that DTP-PDT inhibited cell growth and induced ROS generation in MCF-7 and SGC7901 cells. The ROS scavenger N-acetyl-L-cysteine (NAC) and the P38 MAPK inhibitor SB203580 alleviated DTP-PDT-induced cytotoxicity. DTP-PDT induced cell apoptosis together with upregulated Bax and downregulated Bcl-2, which could also be inhibited by NAC or SB203580. The level of LC3B-II, a marker of autophagy, was increased by DTP-PDT. A total of 3496 DERs were obtained after DTP-PDT. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that DERs included those involved in cytosolic ribosomes, the nuclear lumen, protein binding, cell cycle, protein targeting to the endoplasmic reticulum, and ribosomal DNA replication. Disease Ontology and Reactome enrichment analyses indicated that DERs were associated with a variety of cancers and cell cycle checkpoints. Protein-protein interaction results demonstrated that cdk1 and rps27a ranked in the top 10 interacting genes. Therefore, DTP-PDT could inhibit cell growth and induce cell apoptosis and autophagy, partly through ROS and the P38 MAPK signaling pathway. Genes associated with the cell cycle, ribosomes, DNA replication, and protein binding may be the key changes in DTP-PDT-mediated cytotoxicity. [ABSTRACT FROM AUTHOR]

The purpose of current study was to assess the impact of ALA-coated gold nanoclusters (Au NPs) on the combined therapeutic effects of radiotherapy (RT) and photodynamic therapy (PDT) on healthy MCF-10A and MCF-7 breast cancer cells. The Au NPs were covered with ALA using PEG polymer, resulting in the synthesis of Au@ALA NPs. The successful synthesis of the final NPs was confirmed through FTIR, XRD, TEM, and UV–Vis tests. MCF-10A and MCF-7 cell lines were treated with different concentrations of Au@ALA NPs and exposed to irradiation of 2 and 4 Gy (using MV X-ray) and 630 nm laser light irradiation. Cytotoxicity was assessed using a multifaceted approach involving the MTT assay, real-time PCR, and colony forming assay. The findings revealed that the damage inflicted by Au@ALA NPs on cancerous tissue was significantly greater than that on normal tissue. The cytotoxic effects of all experimental groups exhibited a direct correlation with increasing concentrations and radiation doses. The combination of Au@ALA NPs with RT doses of 2 and 4 Gy resulted in a reduction in cell viability by a factor of 1.58 (P = 0.001) and 1.73 (P = 0.004), respectively. Furthermore, the simultaneous intervention of NPs with PDT and RT at doses of 2 and 4 Gy led to a decrease in cell viability by a factor of 2.10 (P = 0.001) and 3.08 (P = 0.001) in turn. Furthermore, the real-time PCR and colonogenic assay results demonstrated that the combined treatment significantly increased phosphorylation of ATM and expression of TP53, indicating an adequate synergistic effect on breast cancer cells. The concurrent application of Au@ALA NPs in RT and PDT successfully enhanced the radiosensitization of breast cancer cells to megavoltage RT and PDT. [ABSTRACT FROM AUTHOR]

Antimicrobial photodynamic therapy (aPDT) is a promising approach to combat antibiotic resistance in endodontic infections. It eliminates residual bacteria from the root canal space and reduces the need for antibiotics. To enhance its effectiveness, an in silico and in vitro study was performed to investigate the potential of targeted aPDT using natural photosensitizers, Kojic acid and Parietin. This approach aims to inhibit the biofilm formation of Enterococcus faecalis, a frequent cause of endodontic infections, by targeting the Ace and Esp proteins. After determining the physicochemical characteristics of Ace and Esp proteins and model quality assessment, the molecular dynamic simulation was performed to recognize the structural variations. The stability and physical movement of the protein-ligand complexes were evaluated. In silico molecular docking was conducted, followed by ADME/Tox profiling, pharmacokinetics characteristics, and assessment of drug-likeness properties of the natural photosensitizers. The study also investigated the changes in the expression of genes (esp and ace) involved in E. faecalis biofilm formation. The results showed that both Kojic acid and Parietin complied with Lipinski's rule of five and exhibited drug-like properties. In silico analysis indicated stable complexes between Ace and Esp proteins and the natural photosensitizers. The molecular docking studies demonstrated good binding affinity. Additionally, the expression of the ace and esp genes was significantly downregulated in aPDT using Kojic acid and Parietin with blue light compared to the control group. This investigation concluded that Kojic acid and Parietin with drug-likeness could efficiently interact with Ace and Esp proteins with a strong binding affinity. Hence, natural photosensitizers-mediated aPDT can be considered a promising adjunctive treatment against endodontic infections. [ABSTRACT FROM AUTHOR]

Antimicrobial photodynamic therapy (aPDT) has shown efficacy in inactivating different bacterial species by photosensitizer-induced free radical production. Despite aPDT is considered unable to cause resistant strains, enzymatic pathways for detoxification of reactive oxygen species and transmembrane photosensitizer efflux systems could cause resistance to aPDT. Resistance mechanisms can be evaluated by measurement of mRNA from by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Thus, the aim of this study was to access the mRNA level data obtained by RT-qPCR in bacterial cells submitted to photodynamic therapy. Studies performed on mRNA levels in bacteria after PDT were assessed on MEDLINE/Pubmed. The mRNA levels from genes related to various functions have been successfully evaluated in both Gram-positive and -negative bacteria after aPDT by RT-qPCR. Such an approach has improved the understanding of aPDT-induced effects, and reinforced the effectiveness of aPDT on bacteria, which can cause infections in different human tissues. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) combines a light source, oxygen, and a photosensitizer (PS) to generate reactive oxygen species (ROS) for treating diseases. In this study, we evaluated two meso‐tetra‐pyridyl porphyrins with [Pd(bpy)Cl]+, namely 3‐PdTPyP and 4‐PdTPyP, as PS for PDT application. DNA interaction was assessed by spectroscopic measurements (UV–Vis and fluorescence emission), viscosity analysis, and molecular docking simulations. The results indicate that Pd(II)‐porphyrins do not intercalate into DNA, suggesting that the minor groove is the primary interaction site, mainly through van der Waals forces. These metalloporphyrins effectively induced nitrogenous bases oxidation, particularly in purines, after white light irradiation. The induced DNA lesions were able to inactivate plasmid DNA metabolism (DNA replication and transcription) in a bacterial model. 3‐PdTPyP and 4‐PdTPyP significantly decreased the viability of treated melanoma cell lines (A375 and B16‐F10), demonstrating that melanoma cell lines were more sensitive to these Pd(II)‐porphyrins than the fibroblast cell line (L929). Moreover, 3‐PdTPyP was more photototoxic to A375 cells (IC50 = 0.43 μM), whereas 4‐PdTPyP was more photototoxic to B16‐F10 cells (IC50 = 0.51 μM). These findings suggest that these porphyrins are promising PS for future PDT research focused on skin cancer. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) has long been considered an effective way to tackle antibiotic resistance. Here, Methylene blue (MB) as photosensitizer was combined with carbon quantum dots (CQDs) as drug carriers to make a compound antibacterial agent. The fluorescent CQDs were prepared by hydrothermal method with citric acid (CA) and neutral red (NR) as raw materials. The CQDs can emit 640nm red fluorescence under 520nm laser irradiation. In the antibacterial experiment, CQDs-MB was irradiated with 660nm light. The results showed that CQDs-MB had ideal antibacterial activity against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) with 100% antibacterial concentration of 5μM and 10μM, respectively. The combination of CQDs and MB enhanced singlet oxygen (1O2) generation and the PDT activity of MB, which significantly increased the phototoxicity of MB to bacteria. [ABSTRACT FROM AUTHOR]

Antibiotic resistance induced by antibiotic abuse is considered as one of the most serious public health problems. Antibacterial photodynamic therapy (APDT) using an efficient photosensitizer has been gaining increasing attention in recent years owing to its high efficacy and lack of drug resistance. Herein, we reported a photosensitizer system composed of tetra-aminophenyl porphyrin (TAPP) loaded in a guanidinium-based ionic covalent framework (COFTGTp) via π–π interactions to form TAPP/COFTGTp. The aim was to use it for APDT, which will not only solve the problems with TAPP as a photosensitizer, wherein it easily aggregates in aqueous solution and is ineffective against Gram-negative bacteria, but can combine the antibacterial activity of the cationic COFTGTp with the APDT induced by TAPP to achieve optimal antibacterial effects on both Gram-positive and Gram-negative bacteria. After TAPP loading in COFTGTp, the stability of TAPP/COFTGTp in aqueous solution was enhanced compared with TAPP, and the drug-loading efficiency could reach 27%. Under white-light irradiation, TAPP/COFTGTp can be activated to catalyze oxygen conversion into reactive oxygen species (ROS) including singlet oxygen (1O2); this will annihilate bacteria via the full use of the positive charge of cationic COFTGTp, which closes the distance between the bacteria and ROS. In addition, MTT and hemolysis experiments showed that TAPP/COFTGTp was almost noncytotoxic and did not cause hemolysis. Most remarkably, the minimum inhibitory concentrations (MICs) of TAPP/COFTGTp for E. coli and S. aureus were 100 μg mL−1 and 50 μg mL−1, respectively. As a result, TAPP/COFTGTp is expected to be an antibacterial material and have promise for substituting traditional antibiotics to solve antibiotic resistance and the emergence of superbacteria. [ABSTRACT FROM AUTHOR]

ABSTRACT Photodynamic therapy (PDT) has been an effective tumor treatment to reduce the side effects of chemotherapy. Herein, we described the synthesis of two Ru (II) complexes by introducing a phenanthrene unit and their photocytotoxicity. Ru1 and Ru2 displayed high DNA affinities by intercalation. Under light, two complexes produced high singlet oxygen (1O2) quantum yields and cleaved DNA efficiently. Both high DNA affinities and 1O2 quantum yields of two complexes resulted in obvious photocytotoxicity towards Hela, A549, and A375 cells. Furthermore, low dark cytotoxicity was also observed for two complexes, which may promote them to act as potential PDT agents. TDDFT (Time‐dependent density functional theory) calculations also demonstrated two complexes that might display the PDT activities via 1O2 photogeneration. [ABSTRACT FROM AUTHOR]

The synthesis of organic photosensitizers with effective reactive oxygen species (ROS) generation remains one of the urgent needs for cancer therapy. In this study, a simple strategy is developed to endow the intrinsic non‐photosensitizer fluorophores with profound ROS‐generating ability upon light irradiation. This strategy is featured by introducing donor–acceptor (D‐A) structured fluorophores as auxiliary ligands into the Ir(III) metal complex, which provides the Ir(III) metal center‐based triplet state (T1) as an energy level springboard to efficiently enhance the energy transition to the D‐A ligand‐based triplet state (T1'). The energy level difference between T1 and T1' can be regulated through altering the cyclometalated ligands of Ir(III), facilitating the energy transfer from T1 to T1' for augmented ROS generation. To improve the pharmacological properties of the obtained D‐A coordinated Ir(III) complex, it is incorporated with the exosomes extracted from M1 phenotype macrophages (M1‐Exos). The generated nanocomplexes are able to trigger synergistic photodynamic therapy, facilitating the reprogramming of tumor‐associated macrophages and eradicating the tumors in mice. This study provides a general strategy to transform non‐photosensitizer fluorophores into effective photosensitizers for biomedical applications. [ABSTRACT FROM AUTHOR]

Background: Cancer immunotherapy has made significant progress in recent years, with numerous studies worldwide. Immunotherapy has had a transformative impact on oncology and autoimmune diseases. In the biomedical arena, hydrogels with good properties are widely used in cancer immunotherapy. Our study used bibliometrics to analyze the changing trends in using hydrogels for cancer immunotherapy. Methods: From 2013 to 2023, a systematic search was conducted in the Web of Science Core Collection database to identify reviews and articles discussing the applications of hydrogels in cancer immunotherapy. The software CiteSpace was used to visually perform the bibliometric analysis in terms of research trends, countries, institutions, authors, journals, and keywords. Individual authors' productivity was assessed with the Lotka's law. The most relevant publication sources were identified by Bradford's law. Results: A total of 422 English-language publications related to hydrogels in cancer immunotherapy were collected. The number of annual publications increased rapidly after 2021 and remained constant for the past two years. China published the most articles in this field. The institution with the maximum number of published articles was the Chinese Academy of Sciences in China. Chen. Q was the most prolific author, and Liu. Z was the second most published author. In terms of journal contributions, the journal "Biomaterials" had the highest number of publications (n = 30). Biomaterials, Advanced Functional Materials and Journal of Controlled Release were the most influential journals. Keyword analysis revealed that cancer immunotherapy, drug delivery, immunogenic cell death, tumor microenvironment, injectable hydrogels, and immune checkpoint blockade were the primary research hotspots. In recent 3 years, adoptive T-cell therapy, black phosphorus, cell capture, adaptive cell therapy, tumor microenvironment, photodynamic therapy, and sustained release were the research hotspots in this field. Our study summarizes the objective of hydrogels in cancer immunotherapy in recent years, providing a reference for potential researchers in related field. Conclusion: This bibliometric analysis shows the progress and trend of research on hydrogels in cancer immunotherapy. This study provides a significant avenue for future investigation into current concerns and trends in research within this field. [ABSTRACT FROM AUTHOR]