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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]

[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]

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]

Hydrogen peroxide (H2O2) is a versatile oxidant, and its eco-friendly synthesis via visible light and air oxygen is crucial. Anthraquinone compounds were employed as homogeneous photocatalysts for alcohol oxidation, yielding H2O2 under visible light. Instead of using traditional catalyst library screening, a model based on density functional theory was proposed to structurally optimize anthraquinone photocatalysts, resulting in the discovery of a novel catalyst significantly boosting H2O2 generation (up to 621.2 mM h-1 intermittently). Continuous flow reactor design improvements can enhance chemical transformation efficiency, as demonstrated by continuous H2O2 production using 2,6-di-tert-butyl anthraquinone. When isopropanol was used as the hydrogen atom donor, H2O2 production rates reached 3950.6 mM h-1 in a 7-minute reaction, with a space--time yield of 7.90 mol (L h) -1, showcasing promising advancements in green H2O2 synthesis. [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]

Hydrogen‐bonded organic frameworks (HOFs) are outstanding candidates for photocatalytic hydrogen evolution. However, most of reported HOFs suffer from poor stability and photocatalytic activity in the absence of Pt cocatalyst. Herein, a series of metal HOFs (Co2‐HOF‐X, X=COOMe, Br, tBu and OMe) have been rationally constructed based on dinuclear cobalt complexes, which exhibit exceptional stability in the presence of strong acid (12 M HCl) and strong base (5 M NaOH) for at least 10 days. More impressively, by varying the ‐X groups of the dinuclear cobalt complexes, the microenvironment of Co2‐HOF‐X can be modulated, giving rise to obviously different photocatalytic H2 production rates, following the −X group sequence of −COOMe>−Br>−tBu>−OMe. The optimized Co2‐HOF‐COOMe shows H2 generation rate up to 12.8 mmol g−1 h−1 in the absence of any additional noble‐metal photosensitizers and cocatalysts, which is superior to most reported Pt‐assisted photocatalytic systems. Experiments and theoretical calculations reveal that the −X groups grafted on Co2‐HOF‐X possess different electron‐withdrawing ability, thus regulating the electronic structures of Co catalytic centres and proton activation barrier for H2 production, and leading to the distinctly different photocatalytic activity. [ABSTRACT FROM AUTHOR]

Controlling the succession of chemical processes with high specificity in complex systems is advantageous for widespread applications, from biomedical research to drug manufacturing. Despite synthetic advances in bioorthogonal and photochemical methodologies, there is a need for generic chemical approaches that can universally modulate photodynamic reactivity in organic photosensitizers. Herein we present a strategy to fine-tune the production of singlet oxygen in multiple photosensitive scaffolds under the activation of bioresponsive and bioorthogonal stimuli. We demonstrate that the photocatalytic activity of nitrobenzoselenadiazoles can be fully blocked by site-selective incorporation of electron-withdrawing carbamate moieties and restored on demand upon uncaging with a wide range of molecular triggers, including abiotic transition-metal catalysts. We also prove that this strategy can be expanded to most photosensitizers, including diverse structures and spectral properties. Finally, we show that such advanced control of singlet oxygen generation can be broadly applied to the photodynamic ablation of human cells as well as to regulate the release of singlet oxygen in the semi-synthesis of natural product drugs. Generic chemical approaches that can universally modulate photodynamic reactivity in organic photosensitizers are of high interest. Here, the authors present a strategy to fine-tune the production of singlet oxygen in multiple photosensitive scaffolds under the activation of bioresponsive and bioorthogonal stimuli. [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]

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]

Development of multi-, extensively-, and pandrug-resistant (MDR, XDR, and PDR) strains of Pseudomonas aeruginosa remains a major problem in medical care. The present study evaluated the effect of antimicrobial photodynamic therapy (aPDT) as a monotherapy and in combination with colistin against P. aeruginosa isolates. Two P. aeruginosa isolates recovered from patients with respiratory tract infections were examined in this study. Minimum inhibitory concentration (MIC) of colistin was determined by the colistin broth disk elution (CBDE) and the reference broth microdilution (rBMD) methods. aPDT was performed using the photosensitizer (Ps) riboflavin at several concentrations and a light-emitting diode (LED) emitting blue light for different irradiation times with or without colistin at 1/2 × MIC concentration. Both PA1 and PA2 isolates were identified as colistin-resistant P. aeruginosa with a MIC ≥4 μg/mL by the CBDE and MICs of 512 μg/mL and 256 μg/mL, respectively, by the rBMD. In aPDT, neither riboflavin nor LED light alone had antibacterial effects. The values of colony forming units per milliliter (CFU/mL) in both isolates were significantly reduced by LED + Ps treatments in a time-dependent manner (LED irradiation time) and dose-dependent manner (Ps concentration). In comparison with control, treatment with Ps (50 μM) + LED (120 s) and Ps (100 μM) + LED (120 s) resulted in 0.27 log 10 CFU/mL and 0.43 log 10 CFU/mL reductions in PA1, and 0.28 log 10 CFU/mL and 0.34 log 10 CFU/mL reductions in PA2, respectively, (P < 0.01). The best results were obtained after the combination of aPDT followed by colistin, which increased bacterial reduction, resulting in a 0.41−0.7 log 10 CFU/mL reduction for PA1 and 0.35−0.83 log 10 CFU/mL reduction for PA2 (P = 0.001). This study suggests the potential implications of aPDT in combination with antibiotics, such as colistin for treatment of difficult-to-treat P. aeruginosa infections. [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]

The design of near‐infrared photosensitizers with high photodynamic and photothermal synergistic therapeutic properties is of great significance for tumor therapy. In this study, An‐cyclic‐BDP with excellent near‐infrared absorption (ε = 1.94 × 105 m−1 cm−1 at 804 nm) is prepared using a dual strategy of twisted π‐conjugated system induction (T‐π‐CSI) and spin‐orbit charge transfer (SOCT). Theoretical calculations, steady‐state and transient absorption spectra are used to investigate the intrinsic regulatory mechanisms between molecular structure and intersystem crossing (ISC) capacity. The results indicate that the application of the T‐π‐CSI and SOCT approach can be superimposed to increase ISC capacity and the triplet lifetime of An‐cyclic‐BDP (τ = 2961 ps). Electron paramagnetic resonance (EPR) results confirm that An‐cyclic‐BDP has the ability to generate hydroxyl radical (·OH) and singlet oxygen (1O2). Furthermore, the calculated 1O2 yield of An‐cyclic‐BDP is found to be 13%. The experimental results of the photothermal conversion indicates that An‐cyclic‐BDP exhibits a photothermal conversion efficiency of up to 48%. In vitro cell experiments demonstrate that An‐cyclic‐BDP‐NPs, constructed by encapsulating An‐cyclic‐BDP with DSPE‐mPEG2000, exhibit excellent biocompatibility and tumor cell‐killing ability. Therefore, the strong near‐IR absorption photosensitizer prepared in this study exhibits significant potential for application in the area of photodynamic and photothermal synergistic therapy. [ABSTRACT FROM AUTHOR]

Herein, we report a novel flavin analogue as singular chemical component for lysosome bioimaging, and inherited photosensitizer capability of the flavin core was demonstrated as a promising candidate for photodynamic therapy (PDT) application. Fine‐tuning the flavin core with the incorporation of methoxy naphthyl appendage provides an appropriate chemical design, thereby offering photostability, selectivity, and lysosomal colocalization, along with the aggregation‐induced emissive nature, making it suitable for lysosomal bioimaging applications. Additionally, photosensitization capability of the flavin core with photostable nature of the synthesized analogue has shown remarkable capacity for generating reactive oxygen species (ROS) within cells, making it a promising candidate for photodynamic therapy (PDT) application. [ABSTRACT FROM AUTHOR]

Senescence is a cellular response having physiological and reparative functions to preserve tissue homeostasis and suppress tumor growth. However, the accumulation of senescent cells would cause deleterious effects that lead to age‐related dysfunctions and cancer progression. Hence, selective detection and elimination of senescent cells are crucial yet remain a challenge. A β‐galactosidase (β‐gal)‐activated boron dipyrromethene (BODIPY)‐based photosensitizer (compound 1) is reported here that can selectively detect and eradicate senescent cells. It contains a galactose moiety connected to a pyridinium BODIPY via a self‐immolative nitrophenylene linker, of which the photoactivity is effectively quenched. Upon interactions with the senescence‐associated β‐gal, it undergoes enzymatic hydrolysis followed by self‐immolation, leading to the release of an activated BODIPY moiety by which the fluorescence emission and singlet oxygen generation are restored. The ability of 1 to detect and eliminate senescent cells is demonstrated in vitro and in vivo, using SK‐Mel‐103 tumor‐bearing mice treated with senescence‐inducing therapy. The results demonstrate that 1 can be selectively activated in senescent cells to trigger a robust senolytic effect upon irradiation. This study breaks new ground in the design and application of new senolytic agents based on photodynamic therapy. [ABSTRACT FROM AUTHOR]

Activatable type I photosensitizers are an effective way to overcome the insufficiency and imprecision of photodynamic therapy in the treatment of hypoxic tumors, however, the incompletely inhibited photoactivity of pro‐photosensitizer and the limited oxidative phototoxicity of post‐photosensitizer are major limitations. It is still a great challenge to address these issues using a single and facile design. Herein, a series of totally caged type I pro‐photosensitizers (Pro‐I‐PSs) are rationally developed that are only activated in tumor hypoxic environment and combine two oxygen‐independent therapeutic mechanisms under single‐pulse laser irradiation to enhance the phototherapeutic efficacy. Specifically, five benzophenothiazine‐based dyes modified with different nitroaromatic groups, BPN 1−5, are designed and explored as latent hypoxia‐activatable Pro‐I‐PSs. By comparing their optical responses to nitroreductase (NTR), it is identified that the 2‐methoxy‐4‐nitrophenyl decorated dye (BPN 2) is the optimal Pro‐I‐PSs, which can achieve NTR‐activated background‐free fluorescence/photoacoustic dual‐modality tumor imaging. Furthermore, upon activation, BPN 2 can simultaneously produce an oxygen‐independent photoacoustic cavitation effect and a photodynamic type I process at single‐pulse laser irradiation. Detailed studies in vitro and in vivo indicated that BPN 2 can effectively induce cancer cell apoptosis through synergistic effects. This study provides promising potential for overcoming the pitfalls of hypoxic‐tumor photodynamic therapy. [ABSTRACT FROM AUTHOR]

As we all know, cancer is still a disease that we are struggling against. Although the traditional treatment options are still the mainstream in clinical practice, emerging phototheranostics technologies based on photoacoustic or fluorescence imaging-guided phototherapy also provide a new exploration direction for non-invasive, low-risk and highly efficient cancer treatment. Photosensitizers are the core materials to accomplish this mission. Recently, more attention has been paid to the emerging A–D–A fused-ring photosensitizers. A–D–A fused-ring photosensitizers display strong and wide absorption spectra, high photostability and easy molecular modification. Since this type of photosensitizer was first used for tumor therapy in 2019, its application boundaries are constantly expanding. Therefore, in this feature article, from the perspective of molecular design, we focused on the development of these molecules for application in phototheranostics over the past five years. The effects of tiny structural changes on their photophysical properties are discussed in detail, which provides a way for structural optimization of the subsequent A–D–A photosensitizers. [ABSTRACT FROM AUTHOR]

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

The efficient generation of reactive oxygen species (ROS) is crucial for the photodynamic therapy (PDT) effect. The D‐π‐A molecular engineering strategy can effectively separate the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) distribution to achieve a smaller energy gap thereby facilitating ROS generation of photosensitizers (PSs). Incorporating heterocycles as π‐bridges can not only extend the conjugation system with improving the degree of π‐delocalization but also effectively accelerate the intersystem crossing process. Herein, a N‐heterocycle purine is innovatively integrated into the D‐π‐A structure as a π‐bridge, which significantly enhances the photodynamic performance by achieving high levels of Type I and Type II ROS generation. The most potent TPM‐QN2 is obtained by modulating the electron‐withdrawing ability of the acceptor (quinolinium), with a 1O2 yield of 9.32, which is the highest yield reported to date. Furthermore, these purine‐based PSs exhibit excellent capabilities in promoting cell photodynamic ablation and inhibiting tumor tissue growth. This novel approach of introducing natural heterocycles provides a promising avenue for developing high‐performance PSs and promoting tumor phototherapy. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is an effective method for treating microbial infections by leveraging the unique photophysical properties of photosensitizing agents, but issues such as fluorescence quenching and the restricted generation of reactive oxygen species (ROS) under hypoxic conditions still remain. In this study, we successfully synthesized and designed a coumarin-based aggregation-induced emission luminogen (AIEgen), called ICM, that shows a remarkable capacity for type I ROS and type II ROS generation. The 1O2 yield of ICM is 0.839. The ROS it produces include hydroxyl radicals (HO•) and superoxide anions (O2•−), with highly effective antibacterial properties specifically targeting Staphylococcus aureus (a Gram-positive bacterium). Furthermore, ICM enables broad-spectrum fluorescence imaging and exhibits excellent biocompatibility. Consequently, ICM, as a potent type I photosensitizer for eliminating pathogenic microorganisms, represents a promising tool in addressing the threat posed by these pathogens. [ABSTRACT FROM AUTHOR]

Endometrial cancer is the most common malignant tumor of the female reproductive system. It develops in the mucous membrane lining the inside of the uterine body—the endometrium, through the abnormal and continuous growth of cancer cells originating from the uterine mucosa. In recent years, there has been a significant increase in the number of cases in European countries. Photodynamic therapy (PDT) is an innovative and dynamically developing medical procedure, useful in the treatment of cancer and non-cancer tissue conditions. The PDT reaction involves the activation of a photosensitizing substance with visible light, which in turn leads to the formation of free oxygen radicals, which contribute to the destruction of the cell. PDT is minimally invasive, has few side effects, and preserves organ anatomy and function. Both diagnostics and photodynamic therapy as modern methods of treatment are becoming more and more popular in many research units around the world. They are most often practiced and tested in in vitro experimental conditions. In clinical practice, the use of PDT is rare. Comprehensive cooperation between scientists contributes to taking steps towards obtaining new, synthetic photosensitizers, directing their physicochemical properties, and showing the impact on a given organism. This review examines the evidence for the potential and usefulness of PDT in the treatment of endometrial cancer. This review highlights that PDT is gaining popularity and is becoming a promising field of medical research. [ABSTRACT FROM AUTHOR]

Nanobodies (Nbs), the smallest antigen-binding fragments with high stability and affinity derived from the variable domain of naturally occurring heavy-chain-only antibodies in camelids, have been shown as an efficient way to improve the specificity to tumors for photodynamic therapy (PDT). Nonetheless, the rapid clearance of Nbs in vivo restricts the accumulation and retention of the photosensitizer at the tumor site causing insufficient therapeutic outcome, especially in large-volume tumors. Herein, we develop photodynamic conjugates, MNB-Pyra Nbs, through site-specific conjugation between 7D12 Nbs and type I photosensitizer MNB-Pyra (morpholine-modified nile blue structure connected to pyrazolinone) in a 1:2 ratio. The photosensitizers with long-term retention can be released at the tumor site by reactive oxygen species cleavage after illumination, accompanied with fluorescence recovery for self-reporting the occurrence of PDT. Ultimately, a single dose of MNB-Pyra Nbs demonstrate highly effective tumor suppression with high biosafety in the large-volume tumor models after three rounds of PDT. This nanobody conjugate provides a paradigm for the design of precise long-time retention photosensitizers and is expected to promote the development of PDT. Cancer therapy with nanobodies (Nbs) is limited by its effective accumulation at the tumor sites. Here the authors develop a Nile blue-based photosensitizer conjugating with pyrazolone-derived Nbs thereby achieving effective retention on tumor sites and suppressing tumor progression through photodynamic therapy. [ABSTRACT FROM AUTHOR]

The therapeutic efficacy of photosensitizers in photodynamic therapy (PDT) largely depends on the reactive oxygen species production, types, and tissue penetration depth. Particularly in malignant tumors, hypoxia is widely recognized as a major obstacle for PDT. Herein, a two‐photon‐excitable heavy‐atom free photosensitizer PNF is designed. PNF can be used as a type‑I photosensitizer to overcome the limitations of PDT in treating hypoxic tumors. The photosensitizer PNF exhibits distinct aggregation‐induced emission characteristics and can generate O2•− and OH• through type I photochemical processes upon 808 nm laser irradiation. The two‐photon‐activated PDT induced by PNF disrupts cellular redox homeostasis, and increases levels of lipid peroxidation, leading to apoptosis, as well as ferroptosis. In vitro and in vivo experiments demonstrate the effectiveness of this synergistic treatment strategy in inhibiting the growth of hypoxic cancer cells and tumors. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a light-based anticancer therapy that can induce tumor necrosis and/or apoptosis. Two important factors contributing to the efficacy of PDT are the concentration of the photosensitizer in the tumor tissue and its preferential accumulation in the tumor tissue compared to that in normal tissues. In this study, we investigated the use of optical imaging for monitoring whole-body bio-distribution of the fluorescent (660 nm) photosensitizer Bremachlorin in vivo, in a murine pancreatic ductal adenocarcinoma (PDAC) model. Moreover, we non-invasively, examined the induction of tumor necrosis after PDT treatment using near-infrared fluorescent imaging of the necrosis avid cyanine dye IRDye®-800CW Carboxylate. Using whole-body fluorescence imaging, we observed that Bremachlorin preferentially accumulated in pancreatic tumors. Furthermore, in a longitudinal study we showed that 3 hours after Bremachlorin administration, the fluorescent tumor signal reached its maximum. In addition, the tumor-to-background ratio at all-time points was approximately 1.4. Ex vivo, at 6 hours after Bremachlorin administration, the tumor-to-muscle or -normal pancreas ratio exhibited a greater difference than it did at 24 hours, suggesting that, in terms of efficacy, 6 hours after Bremachlorin administration was an effective time point for PDT treatment of PDAC. In vivo administration of the near infrared fluorescence agent IRDye®-800CW Carboxylate showed that PDT, 6 hours after administration of Bremachlorin, selectively induced necrosis in the tumor tissues, which was subsequently confirmed histologically. In conclusion, by using in vivo fluorescence imaging, we could non-invasively and longitudinally monitor, the whole-body distribution of Bremachlorin. Furthermore, we successfully used IRDye®-800CW Carboxylate, a near-infrared fluorescent necrosis avid agent, to image PDT-induced necrotic cell death as a measure of therapeutic efficacy. This study showed how fluorescence can be applied for optimizing, and assessing the efficacy of, PDT. [ABSTRACT FROM AUTHOR]

Zn-Ag-In-S (ZAIS) quantum dots (QDs) were synthesized with various Ag-to-In ratios and used as novel photosensitizers for photodynamic therapy (PDT) on cancer cell inhibition and bacterial sterilization, and their structural, optical, and photodynamic properties were investigated. The alloyed QDs displayed a photoluminescence quantum yield of 72% with a long fluorescence lifetime of 5.3 μs when the Ag-to-In ratio was 1:3, suggesting a good opportunity as a dual functional platform for fluorescence imaging and PDT. The ZAIS QDs were then coated with amphiphilic brush copolymer poly(maleic anhydride-alt-1-octadecene) (PMAO) before application. The 1O2 quantum yield of the ZAIS/PMAO was measured to be 8%, which was higher than previously reported CdSe QDs and comparable to some organic photosensitizers. Moreover, the ZAIS QDs showed excellent stability in aqueous and biological media, unlike organic photosensitizers that tend to degrade over time. The in vitro PDT against human melanoma cell line (A2058) and Staphylococcus aureus shows about 30% inhibition rate upon 20 min light irradiation. Cell staining images clearly demonstrated that co-treatment with ZAIS QDs and light irradiation effectively killed A2058 cells, demonstrating the potential of ZAIS QDs as novel and versatile photosensitizers for PDT in cancer and bacterial treatment, and provides useful information for future designing of QD-based photosensitizers. [ABSTRACT FROM AUTHOR]

The present review explores the underlying mechanisms of phytophotodermatitis, a non-immunologic skin reaction triggered by certain plants followed by exposure to ultraviolet radiation emitted by sunlight. Recent research has advanced our understanding of the pathophysiology of phytophotodermatitis, highlighting the interaction between plant-derived photosensitizing compounds (e.g., furanocoumarins and psoralens) and ultraviolet light leading to skin damage (e.g., erythema, fluid blisters, edema, and hyperpigmentation), identifying these compounds as key contributors to the phototoxic reactions causing phytophotodermatitis. Progress in understanding the molecular pathways involved in the skin's response to these compounds has opened avenues for identifying potential therapeutic targets suitable for the management and prevention of this condition. The review emphasizes the importance of identifying the most common phototoxic plant families (e.g., Apiaceae, Rutaceae, and Moraceae) and plant species (e.g., Heracleum mantegazzianum, Ruta graveolens, Ficus carica, and Pastinaca sativa), as well as the specific phytochemical compounds responsible for inducing phytophototoxicity (e.g., limes containing furocoumarin have been linked to lime-induced photodermatitis), underscoring the significance of recognizing the dangerous plant sources. Moreover, the most used approaches and tests for accurate diagnosis such as patch testing, Wood's lamp examination, or skin biopsy are presented. Additionally, preventive measures such as adequate clothing (e.g., long-sleeved garments and gloves) and treatment strategies based on the current knowledge of phytophotodermatitis including topical and systemic therapies are discussed. Overall, the review consolidates recent findings in the field, covering a diverse array of phototoxic compounds in plants, the mechanisms by which they trigger skin reactions, and the implications for clinical management. By synthesizing these insights, we provide a comprehensive understanding of phytophotodermatitis, providing valuable information for both healthcare professionals and researchers working to address this condition. [ABSTRACT FROM AUTHOR]

Modular nanotransporters (MNTs) are drug delivery systems for targeted cancer treatment. As MNTs are composed of several modules, they offer the advantage of high specificity and biocompatibility in delivering drugs to the target compartment of cancer cells. The large carrier module brings together functioning MNT modules and serves as a platform for drug attachment. The development of smaller-sized MNTs via truncation of the carrier module appears advantageous in facilitating tissue penetration. In this study, two new MNTs with a truncated carrier module containing either an N-terminal (MNTN) or a C-terminal (MNTC) part were developed by genetic engineering. Both new MNTs demonstrated a high affinity for target receptors, as revealed by fluorescent-labeled ligand-competitive binding. The liposome leakage assay proved the endosomolytic activity of MNTs. Binding to the importin heterodimer of each truncated MNT was revealed by a thermophoresis assay, while only MNTN possessed binding to Keap1. Finally, the photodynamic efficacy of the photosensitizer attached to MNTN was significantly higher than when attached to either MNTC or the original MNTs. Thus, this work reveals that MNT's carrier module can be truncated without losing MNT functionality, favoring the N-terminal part of the carrier module due to its ability to bind Keap1. [ABSTRACT FROM AUTHOR]

Using plant extracts as photosensitizers in photodynamic therapy (PDT) represents a significant green approach toward sustainability. This study investigates beetroot juice (BRJ), betanin, and their liposomal formulations (Lip-BRJ, Lip-Bet) as photosensitizers in cancer PDT. BRJ was prepared, and its betanin content was quantified via HPLC. The p-nitrosodimethylaniline (RNO)/imidazole technique monitored the singlet oxygen formation. BRJ and betanin decreased the RNO absorbance at 440 nm by 12% and 9% after 45 min of irradiation, respectively. Furthermore, betanin interaction with Bcl-2 proteins was examined using binding free energy analysis and molecular dynamic simulation. The results revealed favorable interactions with ΔG values of −40.94 kcal/mol. Then, BRJ, betanin, Lip-BRJ, and Lip-Bet were tested as photosensitizers on normal (HEK 293) and human lung cancer (A549) cell lines. Irradiation significantly enhanced the cytotoxicity of Lip-Bet on HEK 293 cells (20% cell viability at 2000 µg/mL) and A549 cells (13% cell viability at 1000 µg/mL). For Lip-BRJ, irradiation significantly enhanced the cytotoxicity on HEK 293 cells at lower concentrations and on A549 cells at all tested concentrations. These results proved the positive effect of light and liposomal encapsulation on the anticancer activity of betanin and BRJ, suggesting the efficiency of liposomal beetroot pigments as green photosensitizers. [ABSTRACT FROM AUTHOR]

The replacement of pyridyl by pyrazinyl in ligands of polypyridyl‐based cobalt water reducing catalysts (WRC) shifts reduction potentials anodically. Together with a new, trinuclear ReI photosensitizer, these WRCs show strongly improved photocatalytic performances in turnover numbers (TONs) and maximal H2 evolution rate. Depending on the catalyst structure, up to 65 kTONs at 1 μM WRC concentration were reached. Under electrocatalytic conditions in both DMF and H2O, one of the reported WRCs displays remarkable stability, producing H2 steadily over 21 and 14 d, respectively. [ABSTRACT FROM AUTHOR]

In oxygen (O2)‐dependent photodynamic therapy (PDT), photosensitizers absorb light energy, which is then transferred to ambient O2 and subsequently generates cytotoxic singlet oxygen (1O2). Therefore, the availability of O2 and the utilization efficiency of generated 1O2 are two significant factors that influence the effectiveness of PDT. However, tumor microenvironments (TMEs) characterized by hypoxia and limited utilization efficiency of 1O2 resulting from its short half‐life and short diffusion distance significantly restrict the applicability of PDT for hypoxic tumors. To address these challenges, numerous macromolecular nano‐assemblies (MNAs) have been designed to relieve hypoxia, utilize hypoxia or enhance the utilization efficiency of 1O2. Herein, we provide a comprehensive review on recent advancements achieved with MNAs in enhancing the effectiveness of O2‐dependent PDT against hypoxic tumors. [ABSTRACT FROM AUTHOR]

Metal‐organic frameworks (MOFs) and metal‐organic cages (MOCs) have garnered significant attention as promising photocatalysts due to their tunable chemical structures and integrated multifunctionality. To increase the photocatalytic efficiency, strategies like ligand functionalization, introducing additional catalytic sites, and doping or encapsulating photosensitizers have been explored for both MOFs and MOCs. This concept review focuses on recent advancements in utilizing MOFs and MOCs for photocatalytic hydrogen production, highlighting their unique characteristics and introducing their respective mechanisms in this field. Moreover, it outlines the current challenges and prospects faced by MOFs and MOCs, offering an outlook on their future in this domain. [ABSTRACT FROM AUTHOR]

Porphyrins were identified some years ago as a promising, easily accessible, and tunable class of organic photoredox catalysts, but a systematic study on the effect of the electronic nature and of the position of the substituents on both the ground-state and the excited-state redox potentials of these compounds is still lacking. We prepared a set of known functionalized porphyrin derivatives containing different substituents either in one of the meso positions or at a β-pyrrole carbon, and we determined their ground- and (singlet) excited-state redox potentials. We found that while the estimated singlet excited-state energies are essentially unaffected by the introduction of substituents, the redox potentials (both in the ground- and in the singlet excited-state) depend on the electron-withdrawing or electron-donating nature of the substituents. Thus, the presence of groups with electron-withdrawing resonance effects results in an enhancement of the reduction facility of the photocatalyst, both in the ground and in the excited state. We next prepared a second set of four previously unknown meso-substituted porphyrins, having a benzoyl group at different positions. The reduction facility of the porphyrin increases with the proximity of the substituent to the porphine core, reaching a maximum when the benzoyl substituent is introduced at a meso position. [ABSTRACT FROM AUTHOR]

Triplet‐triplet annihilation upconversion (TTA‐UC) has made significant progress in recent years in several key applications, including solar energy harvesting, photocatalysis, stereoscopic 3D printing, and disease therapeutics. In TTA‐UC research, photosensitizers serve the vital function of harvesting low‐energy photons. The photophysical characteristics of photosensitizers, including absorbance, triplet state quantum yield, triplet state energy level, triplet state lifetime, etc. determine the performance of TTA‐UC. Thus, the study of photosensitizers has been a key aspect of TTA‐UC. In recent years, multi‐resonance thermally activated delayed fluorescence (MR‐TADF) molecules have received extensive attention due to their excellent photophysical properties and electroluminescent device performance. MR‐TADF molecules not only present a narrow energy gap between the singlet and triplet excited states, but also have stronger absorption and better wavelength regulation than conventional TADF molecules. Nowadays, the preliminary attempts in TTA‐UC using MR‐TADF molecules as photosensitizers have resulted in the development of green to ultraviolet, blue to ultraviolet, and even near‐infrared to blue emission. This concept will summarize the research progress of MR‐TADF molecules as photosensitizers in TTA‐UC, analyzing the challenges and giving possible solutions. Finally, we prospect the future development of MR‐TADF molecules as photosensitizers, including the molecular design as well as the possible application areas. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) presents an escalating global challenge as conventional antibiotic treatments become less effective. In response, photodynamic therapy (PDT) and photothermal therapy (PTT) have emerged as promising alternatives. While rooted in ancient practices, these methods have evolved with modern innovations, particularly through the integration of lasers, refining their efficacy. PDT harnesses photosensitizers to generate reactive oxygen species (ROS), which are detrimental to microbial cells, whereas PTT relies on heat to induce cellular damage. The key to their effectiveness lies in the utilization of photosensitizers, especially when integrated into nano- or micron-scale supports, which amplify ROS production and enhance antimicrobial activity. Over the last decade, carbon dots (CDs) have emerged as a highly promising nanomaterial, attracting increasing attention owing to their distinctive properties and versatile applications, including PDT and PTT. They can not only function as photosensitizers, but also synergistically combine with other photosensitizers to enhance overall efficacy. This review explores the recent advancements in CDs, underscoring their significance and potential in reshaping advanced antimicrobial therapeutics. [ABSTRACT FROM AUTHOR]

Over the past decades, medicine has made enormous progress, revolutionized by modern technologies and innovative therapeutic approaches. One of the most exciting branches of these developments is photodynamic therapy (PDT). Using a combination of light of a specific wavelength and specially designed photosensitizing substances, PDT offers new perspectives in the fight against cancer, bacterial infections, and other diseases that are resistant to traditional treatment methods. In today's world, where there is a growing problem of drug resistance, the search for alternative therapies is becoming more and more urgent. Imagine that we could destroy cancer cells or bacteria using light, without the need to use strong chemicals or antibiotics. This is what PDT promises. By activating photosensitizers using appropriately adjusted light, this therapy can induce the death of cancer or bacterial cells while minimizing damage to surrounding healthy tissues. In this work, we will explore this fascinating method, discovering its mechanisms of action, clinical applications, and development prospects. We will also analyze the latest research and patient testimonies to understand the potential of PDT for the future of medicine. [ABSTRACT FROM AUTHOR]

Currently three major problems seriously limit the practical application of cancer photodynamic therapy (PDT): (i) the hypoxic tumor microenvironment (TME); (ii) low generation efficiency of toxic reactive oxygen species (ROS) in aggregates and (iii) shallow tissue penetration depth of excitation light. Very limited approaches are available for addressing all the above three problems with a single design. Herein, a rational "three birds with one stone" molecular and nanoengineering strategy is demonstrated: a photodynamic nanoplatform U‐Ir@PAA‐ABS based on the covalent combination of lanthanide‐doped upconversion nanoparticles (UCNPs) and an AIE‐active dinuclear Ir(III) complex provides a low oxygen concentration‐dependent type‐I photochemical process upon 980 nm irradiation by Föster resonance energy transfer (FRET). U‐Ir@PAA‐ABS targets mitochondria and has excellent phototoxicity even in severe hypoxia environments upon 980 nm irradiation, inducing a dual‐mode cell death mechanism by apoptosis and ferroptosis. Taken together, the in vitro and in vivo results demonstrate a successful strategy for improving the efficacy of PDT against hypoxic tumors. [ABSTRACT FROM AUTHOR]

Aggregate‐level photodynamic therapy (PDT) has attracted significant interest and driven substantial advances in multifunction phototheranostic platforms. As exemplified by two typical instances of aggregation‐caused quenching of reactive oxygen species (ROS) and aggregation‐induced generation of ROS, the aggregation effect plays a significant role on the ROS generation of photosensitizers (PSs), which is worthy of in‐depth exploration and full utilization. However, in contrast to the well‐developed researches on the aggregation effect on luminescence, the studies concerning the aggregation effect on ROS generation are currently in a relatively nascent and disjointed stage, lacking guidance from a firmly established research paradigm. To advance this regard, this review aims at providing a consolidated overview of the fundamental principles and research status of aggregation effects on the ROS generation. Here, the research status can be organized into two main facets. One involves the comparison between isolated state and aggregated state, which is mainly conducted by two methods of changing solvent environments and adding adjuvants into a given solvent. The other underscores the distinctions between different aggregate states, consisting of three parts, namely comparison within the same or between different categories based on the classification of single‐component and multicomponent aggregates. In this endeavor, we will present our views on current research methodologies that explore how aggregation affects ROS generation and highlight the design strategies to leverage the aggregation effect to optimize PS regiments. We aspire this review to propel the advancement of phototheranostic platforms and accelerate the clinical implementation of precision medicine, and inspire more contributions to aggregate‐level photophysics and photochemistry, pushing the aggregate science and materials forward. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is an emerging treatment modality that utilizes light-sensitive compounds, known as photosensitizers, to produce reactive oxygen species (ROS) that can selectively destroy malignant or diseased tissues upon light activation. This study investigates the incorporation of two porphyrin structures, 5-(4-hydroxy-3-methoxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl) porphyrin (P2.2.) and 5,10,15,20-tetrakis-(4-acetoxy-3-methoxyphenyl) porphyrin (P2.1.), into hydroxypropyl cellulose (HPC) hydrogels for potential use in topical photodynamic therapy (PDT). The structural and compositional properties of the resulting hydrogels were characterized using advanced techniques such as Fourier-transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), thermogravimetric analysis (TGA), atomic force microscopy (AFM), UV-Visible (UV-Vis) spectroscopy, and fluorescence spectroscopy. FTIR spectra revealed a slight shift of the main characteristic absorption bands corresponding to the porphyrins and their interactions with the HPC matrix, indicating successful incorporation and potential hydrogen bonding. XRD patterns revealed the presence of crystalline domains within the HPC matrix, indicating partial crystallization of the porphyrins dispersed within the amorphous polymer structure. TGA results indicated enhanced thermal stability of the HPC–porphyrin gels compared to 10% HPC gel, with additional weight loss stages corresponding to the thermal degradation of the porphyrins. Rheological analysis showed that the gels exhibited pseudoplastic behavior and thixotropic properties, with minimal impact on the flow properties of HPC by P2.1., but notable changes in viscosity and shear stress with P2.2. incorporation, indicating structural modifications. AFM imaging revealed a homogeneous distribution of porphyrins, and UV-Vis and fluorescence spectroscopy confirmed the retention of their photophysical properties. Pharmacotechnical evaluations showed that the hydrogels possessed suitable mechanical properties, optimal pH, high swelling ratios, and excellent spreadability, making them ideal for topical application. These findings suggest that the porphyrin-incorporated HPC hydrogels have significant potential as effective therapeutic agents for topical applications. [ABSTRACT FROM AUTHOR]

Microbial infections caused by bacteria, viruses, and fungi pose significant global health threats in diverse environments. While conventional disinfection methods are effective, their reliance on frequent chemical applications raises concerns about resistance and environmental impact. Photodynamic self-disinfecting surfaces have emerged as a promising alternative. These surfaces incorporate photosensitizers that, when exposed to light, produce reactive oxygen species to target and eliminate microbial pathogens. This review explores the concept and mechanism of photodynamic self-disinfecting surfaces, highlighting the variety and characteristics of photosensitizers integrated into surfaces and the range of light sources used across different applications. It also highlights the effectiveness of these surfaces against a broad spectrum of pathogens, including bacteria, viruses, and fungi, while also discussing their potential for providing continuous antimicrobial protection without frequent reapplication. Additionally, the review addresses both the advantages and limitations associated with photodynamic self-disinfecting surfaces and concludes with future perspectives on advancing this technology to meet ongoing challenges in infection control. [ABSTRACT FROM AUTHOR]

Healthcare‐associated infections remain a significant health concern, particularly with the emergence of antibiotic resistance. While these antibiotics have saved countless lives, their overuse reduces their efficacy promoting the emergence of multidrug‐resistant (MDR) bacteria. This prompts researchers to explore new alternatives for treating bacteria proliferation. In this context, antibacterial photodynamic therapy (aPDT) has emerged as a promising approach for treating localized infections. It utilizes reactive oxygen species (ROS) as oxidative stress agents, thereby minimizing the risk of developing MDR. The success of aPDT significantly hinges on the careful selection of photosensitizers (PSs) and polymer matrices for the synthesis of polymer‐based photoactive materials. Various light‐absorbing PSs are therefore designed for enhancing ROS production and antimicrobial efficacy. By incorporating PSs into polymer matrices, these materials can harness the light power to generate ROS, destroying bacterial cells upon irradiation. This review aims to provide a comprehensive overview of advancements in this field, specifically focusing on the use of polymer‐based materials. The mechanism of the four main ROS generated in aPDT, the methods used for their detection, and their mode of action against bacteria has been outlined. The recent improvement in polymer‐based aPDT materials and their antibacterial efficacy have been also addressed. [ABSTRACT FROM AUTHOR]

Three iridium(III) complexes were designed with the purpose of elucidating the photo-physicochemical properties of iridium(III) complexes with narrow band gap at the electronic level. This study indicates that increasing the ligand rigidity and electron delocalization of the compounds can suppress the ring-stretching vibrations of the iridium(III) complex, thus improving their photo-chemical activity and photocytotoxicity. [ABSTRACT FROM AUTHOR]

Photochemical internalization is an efficient strategy relying on photodynamic reactions to promote siRNA endosomal escape for the success of RNA‐interference gene regulation, which makes gene‐photodynamic combined therapy highly synergistic and efficient. However, it is still desired to explore capable carriers to improve the delivery efficiency of the immiscible siRNA and organic photosensitizers simultaneously. Herein, we employ a micellar nanostructure (PSNA) self‐assembled from polymer‐DNA molecular chimeras to fulfill this task. PSNA can plentifully load photosensitizers in its hydrophobic core simply by the nanoprecipitation method. Moreover, it can organize siRNA self‐assembly by the densely packed DNA shell, which leads to a higher loading capacity than the typical electrostatic condensation method. The experimental results prove that this PSNA carrier can greatly facilitate siRNA escape from the endosome/lysosome and enhance transfection. Accordingly, the PSNA‐administrated therapy exhibits a significantly improved anti‐tumor efficacy owing to the highly efficient co‐delivery capability. [ABSTRACT FROM AUTHOR]

Photodynamic therapy is an anti‐cancer treatment that requires illumination of photosensitizers to induce local cell death. Current near‐infrared organic photosensitizers are built from large and non‐modular structures that cannot be tuned to improve safety and minimize off‐target toxicity. This work describes a novel chemical platform to generate enzyme‐activatable near‐infrared photosensitizers. We optimized the Se‐bridged hemicyanine scaffold to include caging groups and biocompatible moieties, and generated cathepsin‐triggered photosensitizers for effective ablation of human glioblastoma cells. Furthermore, we demonstrated that enzyme‐activatable Se‐bridged hemicyanines are effective photosensitizers for the safe ablation of microtumors in vivo, creating new avenues in the chemical design of targeted anti‐cancer photodynamic therapy agents. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a rapidly growing discipline that is expected to become an encouraging noninvasive therapeutic strategy for cancer treatment. In the PDT process, an efficient intersystem crossing (ISC) process for photosensitizers from the singlet excited state (S1) to the triplet excited state (T1) is critical for the formation of cytotoxic reactive oxygen species and improvement of PDT performance. Thermally activated delayed fluorescence (TADF) molecules featuring an extremely small singlet–triplet energy gap and an efficient ISC process represent an enormous breakthrough for the PDT process. Consequently, the development of advanced TADF photosensitizers has become increasingly crucial and pressing. The most recent developments in TADF photosensitizers aimed at enhancing PDT efficiency for bio‐applications are presented in this review. TADF photosensitizers with water dispersibility, targeting ability, activatable ability, and two‐photon excitation properties are highlighted. Furthermore, the future challenges and perspectives of TADF photosensitizers in PDT are proposed. [ABSTRACT FROM AUTHOR]

Antimicrobial Photodynamic Therapy (aPDT) is an innovative and promising method for combating infections, reducing the risk of antimicrobial resistance compared to traditional antibiotics. Squaraine (SQ) dyes can be considered promising photosensitizers (PSs) but are generally hydrophobic molecules that can self-aggregate under physiological conditions. To overcome these drawbacks, a possible solution is to incorporate SQs inside nanoparticles (NPs). The present work deals with the design and development of innovative nanophotosensitizers based on poly lactic-co-glycolic acid (PLGA) NPs incorporating a brominated squaraine (BrSQ) with potential application in aPDT. Two designs of experiments (DoEs) based on the single emulsion and nanoprecipitation methods were set up to investigate how different variables (type of solvent, solvent ratio, concentration of PLGA, stabilizer and dye, sonication power and time) can affect the size, zeta (ζ)-potential, yield, entrapment efficiency, and drug loading capacity of the SQ-PLGA NPs. SQ-PLGA NPs were characterized by NTA, FE-SEM, and UV-Vis spectroscopy and the ability to produce reactive oxygen species (ROS) was evaluated, proving that ROS generation ability is preserved in SQ-PLGA. In vitro antimicrobial activity against Gram-positive bacteria in planktonic state using Staphylococcus aureus was conducted in different conditions and pH to evaluate the potential of these nanophotosensitizers for aPDT in the local treatment of infections. [ABSTRACT FROM AUTHOR]

Self-oxidative degradation photosensitizers capable of bacterial agglutination and membrane insertion were fabricated based on a simple co-assembly strategy, for efficiently killing P. aeruginosa and rapidly deactivating their function post-treatment. [ABSTRACT FROM AUTHOR]

Background: Medicinal plant-mediated combinational therapies have gained importance globally due to minimal side effects and enhanced treatment outcomes compared to single-drug modalities. We aimed to analyze the cytotoxic potential of each conventional treatment i.e., photodynamic therapy (PDT), chemotherapy (doxorubicin hydrochloride; Dox-HCl) with or without various concentrations of medicinal plant extracts (PE) on soft tissue cancer Rhabdomyosarcoma (RD) cell line. Methods: The Rhabdomyosarcoma (RD) cell line was cultured and treated with Photosensitizer (Photosense (AlPc4)), Chemo (Dox-HCl), and their combinations with different concentrations of each plant extract i.e., Thuja occidentalis, Moringa oleifera, Solanum surattense. For the source of illumination, a Diode laser (λ = 630 nm ± 1 nm, Pmax = 1.5 mW) was used. Photosensitizer uptake time (∼ 45 min) was optimized through spectrophotometric measurements (absorption spectroscopy). Drug response of each treatment arm was assessed post 24 h of administration using 3-(4, 5-dimethyl-2-thiazolyl)-2, 5- 5-diphenyl-2 H- tetrazolium bromide (MTT) assay. Results: PE-mediated Chemo-Photodynamic therapy (PDT) exhibited synergistic effects (CI < 1). Moreover, Rhabdomyosarcoma culture pretreated with various plant extracts for 24 h exhibited significant inhibition of cell viability however most effective outcomes were shown by low and high doses of Moringa oleifera compared to other plant extracts. Post low doses treated culture with all plant extracts followed by PDT came up with more effectiveness when compared to all di-therapy treatments. Conclusion: The general outcome of this work shows that the ethanolic plant extracts (higher doses) promote the death of cancerous cells in a dose-dependent way and combining Dox-HCl and photo-mediated photodynamic therapy can yield better therapeutic outcomes. [ABSTRACT FROM AUTHOR]

The Psoralen (Pso) molecule finds extensive applications in photo‐chemotherapy, courtesy of its triplet state forming ability. Sulfur and selenium replacement of exocyclic carbonyl oxygen of organic chromophores foster efficient triplet harvesting with near unity triplet quantum yield. These triplet‐forming photosensitizers are useful in Photodynamic Therapy (PDT) applications for selective apoptosis of cancer cells. In this work, we have critically assessed the effect of the sulfur and selenium substitution at the exocyclic carbonyl (TPso and SePso, respectively) and endocyclic oxygen positions of Psoralen. It resulted in a significant redshifted absorption spectrum to access the PDT therapeutic window with increased oscillator strength. The reduction in singlet‐triplet energy gap and enhancement in the spin‐orbit coupling values increase the number of intersystem crossing (ISC) pathways to the triplet manifold, which shortens the ISC lifetime from 10−5 s for Pso to 10−8 s for TPso and 10−9 s for SePso. The intramolecular photo‐induced electron transfer process, a competitive pathway to ISC, is also considerably curbed by exocyclic functionalizations. In addition, a maximum of 115 GM of two‐photon absorption (2PA) with IR absorption (660–1050 nm) confirms that the Psoralen skeleton can be effectively tweaked via single chalcogen atom replacement to design a suitable PDT photosensitizer. [ABSTRACT FROM AUTHOR]

Photosensitizers that are good producers of singlet oxygen, and the photocatalytic reactions promoted by these photosensitizers, have always been of great interest. In this study, we aimed to develop new photosensitizers based on cyclotriphosphazene and evaluate their performance in photocatalytic reactions. In this context, three new cyclotriphosphazene derivatives, each bearing BODIPY and thiophene units, were synthesized, and their molecular structures were characterized using spectroscopic techniques. Both the BODIPY derivatives and their cyclotriphosphazene derivatives had absorption in the visible region, and also, the resulting cyclotriphosphazene compounds exhibited significantly better molar absorption coefficients compared to the precursor BODIPY units. Incorporation of the halogen atom into the molecules resulted in the redshift of absorption and emission maxima, as well as decrease in the fluorescence characteristics of these molecules. The singlet oxygen-producing abilities of the molecules were evaluated by the chemical trapping method using DPBF as the singlet oxygen scavenger molecule, and the change was monitored by UV-vis absorption spectroscopy. Cyclotriphosphazene compounds 7 and 8 performed significantly better than both methylene blue and their precursor units, with singlet oxygen quantum yield values of 0.85 and 0.91. Finally, the ability of these compounds to convert 1,3-cyclohexadiene into peroxides (2,3-dioxabicyclo[2.2.2]oct-5-ene and 3-hydroperoxycyclohexa-1,4-diene) was evaluated. The compounds displayed notable photocatalytic activity toward the oxidation of 1,3-cyclohexadiene compared to tetraphenyl porphyrin (TPP), a known photocatalyst. [ABSTRACT FROM AUTHOR]

Lanthanide‐doped upconversion nanoparticles (UCNPs) have attractive emission properties but suffer from weak light‐absorbing capacities and thereby relatively low brightnesses. This motivates using strongly absorbing dye molecules as antennas and sensitizers. However, despite much effort, understanding of this dye‐UCNP interplay is still limited. Major sensitization mechanisms are still under discussion, largely because there is a lack of effective means to observe key factors such as dark state transitions within the dyes. Here, a combined spectroscopic procedure is established to systematically investigate the photophysics behind the dye‐UCNP interaction, embracing fluorescence‐based transient‐state excitation‐modulation, lifetime and correlation spectroscopy, and spectrofluorometry/spectrophotometry. With this procedure the heptamethine cyanine dye IR806, a typical UCNP sensitizer is studied, its photophysical model is established, its photophysics in UCL‐sensitization‐related environments is deciphered, and the energy transfer from the IR806 singlet excited state to Yb3+ (UCNP sensitizer ion) can be identified as the dominant sensitization mechanism. These studies suggest that IR806 can form non‐emissive H‐aggregates at the nanoparticle surfaces, which can be dissociated after certain light excitation duration (typically>100 µs). Moreover, buildup of a non‐fluorescent, photo‐redox state of IR806 after longer irradiation times (10–100 ms) can deleteriously affect its UCL sensitization effect, inferring an optimal excitation duration for dye‐sensitized UCNPs, relevant for, e.g., optical imaging applications. [ABSTRACT FROM AUTHOR]

The photophysical properties and efficiency of photosensitized singlet oxygen formation by meso-tetrakis(4- N-methylpyridyl)porphyrin in a complex with hydroxyapatite nanoparticles were studied. At least three types of complexes characterized by different access of oxygen to porphyrin molecules were shown to form on the surface of the hydroxyapatite nanoparticles. Rotation of the pyridyl substituents of porphyrin in the complex with hydroxyapatite nanoparticles was found to be significantly hindered, while porphyrin molecules on the surface of the nanoparticles were in a less polar environment than in water. The quantum yield of photosensitized singlet oxygen formation was observed to decrease by at least nine times for porphyrin in the complex with hydroxyapatite nanoparticles. Porphyrin was released from hydroxyapatite nanoparticles and the efficiency of singlet oxygen formation increased although it did not reach the values characteristic for free porphyrin if the pH decreased to less than 5.0 (pH < 5.0). [ABSTRACT FROM AUTHOR]