Photosensitizing Activity Research Articles

Highlighting the Phototherapeutical Potential of Fungal Pigments in Various Fruiting Body Extracts with Informed Feature-Based Molecular Networking.

Fungal pigments are characterized by a diverse set of chemical backbones, some of which present photosensitizer-like structures. From the genus Cortinarius, for example, several biologically active photosensitizers have been identified leading to the hypothesis that photoactivity might be a more general phenomenon in the kingdom Fungi. This paper aims at testing the hypothesis. Forty-eight fruiting body-forming species producing pigments from all four major biosynthetic pathways (i.e., shikimate-chorismate, acetate-malonate, mevalonate, and nitrogen heterocycles) were selected and submitted to a workflow combining in vitro chemical and biological experiments with state-of-the-art metabolomics. Fungal extracts were profiled by high-resolution mass spectrometry and subsequently explored by spectral organization through feature-based molecular networking (FBMN), including advanced metabolite dereplication techniques. Additionally, the photochemical properties (i.e., light-dependent production of singlet oxygen), the phenolic content, and the (photo)cytotoxic activity of the extracts were studied. Different levels of photoactivity were found in species from all four metabolic groups, indicating that light-dependent effects are common among fungal pigments. In particular, extracts containing pigments from the acetate-malonate pathway, e.g., extracts from Bulgaria inquinans, Daldinia concentrica, and Cortinarius spp., were not only efficient producers of singlet oxygen but also exhibited photocytotoxicity against three different cancer cell lines. This study explores the distribution of photobiological traits in fruiting body forming fungi and highlights new sources for phototherapeutics.

Phototoxic Potential of Different DNA Intercalators for Skin Cancer Therapy: In Vitro Screening.

Photodynamic therapy is a minimally invasive procedure used in the treatment of several diseases, including some types of cancer. It is based on photosensitizer molecules, which, in the presence of oxygen and light, lead to the formation of reactive oxygen species (ROS) and consequent cell death. The selection of the photosensitizer molecule is important for the therapy efficiency; therefore, many molecules such as dyes, natural products and metallic complexes have been investigated regarding their photosensitizing potential. In this work, the phototoxic potential of the DNA-intercalating molecules-the dyes methylene blue (MB), acridine orange (AO) and gentian violet (GV); the natural products curcumin (CUR), quercetin (QT) and epigallocatechin gallate (EGCG); and the chelating compounds neocuproine (NEO), 1,10-phenanthroline (PHE) and 2,2'-bipyridyl (BIPY)-were analyzed. The cytotoxicity of these chemicals was tested in vitro in non-cancer keratinocytes (HaCaT) and squamous cell carcinoma (MET1) cell lines. A phototoxicity assay and the detection of intracellular ROS were performed in MET1 cells. Results revealed that the IC50 values of the dyes and curcumin in MET1 cells were lower than 30 µM, while the values for the natural products QT and EGCG and the chelating agents BIPY and PHE were higher than 100 µM. The IC50 of MB and AO was greatly affected by irradiation when submitted to 640 nm and 457 nm light sources, respectively. ROS detection was more evident for cells treated with AO at low concentrations. In studies with the melanoma cell line WM983b, cells were more resistant to MB and AO and presented slightly higher IC50 values, in line with the results of the phototoxicity assays. This study reveals that many molecules can act as photosensitizers, but the effect depends on the cell line and the concentration of the chemical. Finally, significant photosensitizing activity of acridine orange at low concentrations and moderate light doses was demonstrated.

Antimicrobial photodynamic therapy with Ligularia fischeri against methicillin-resistant Staphylococcus aureus infection in Caenorhabditis elegans model

The high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) infection threatens the effectiveness of current clinical settings. Antimicrobial photodynamic therapy (APDT) is a promising alternative to antibiotics for treating infections due to its low resistance. This study aimed to evaluate the antibacterial properties of APDT with L. fischeri extract (LFE) against MRSA and various skin and oral pathogens in vitro and its photopharmaceutical actions in Caenorhabditis elegans. The antimicrobial activities of APDT with LFE against pathogens were evaluated using plate counting method. The chemical profile was characterized using high-performance liquid chromatography and spectrophotometry. The growth rate assay, lifespan assay, and bacterial attachment on worms were performed to assess the therapeutics effects in C. elegans. The swab method was used for the detection of pathogens on the micropig skin surface. The APDT treatment with L. fischeri extract (LFE, 20 µg/mL) and red light (intensity of 120 W/m2) reduced 4.3–4.9 log (colony forming unit/mL) of Staphylococcus aureus, MRSA, Cutibacterium acnes, Streptococcus mutans; and 2.4 log (CFU/mL) of Candida albicans. Chemical analysis revealed that LFE enriched three active photosensitizers. APDT reduced bacterial populations on worms, recovered growth retardation, and improved lifespan in MRSA-infected C. elegans without causing severe side effects. The surface eradication of MRSA after exposure to LFE with red light was demonstrated on micropig skin. These findings highlight the significance of L. fischeri as a natural resource for the safe phototreatment of MRSA infection in the biomedical and cosmeceutical industries.

Effects of metalation on the PDT activity of arene ruthenium porphyrin-based photosensitizers

Effects of metalation on the PDT activity of arene ruthenium porphyrin-based photosensitizers

Effective fluence and dose at skin depth of daylight and lamp sources for PpIX-based photodynamic therapy.

Skin-based photodynamic therapy (PDT) is used for the clinical treatment of actinic keratosis (AKs) and other skin lesions with continued expansion into the standard of care. Due to the spectral dependency of photosensitizer activation and skin optical fluence, there is a need for more accurate methods to estimate the delivered dose at depth from different PDT light sources and treatment regimens. Develop radiometric methods for calculating photosensitizer-effective fluence and dose at depth and determine differences between red-lamp, blue-lamp, and daylight-based PDT treatments. Radiometric measurements of FDA-approved PDT lamp sources, outdoor daylight, and indoor daylight were performed for clinically relevant AK treatments. The protoporphyrin IX (PpIX) equivalent irradiance, fluence, and dose for each light source were calculated from the PpIX absorption spectrum and a 7-layer skin fluence model. The effective fluence and dose at depth was estimated by combining the spectral attenuation predicted at each wavelength and depth with the source fluence at each wavelength. The red-lamp source had the highest illuminance (112,000lumen/m2), but lowest PpIX-effective irradiance (9.6W/m2), and highest effective fluence at depth (10.8W/m2 at 500µm). In contrast, the blue light source had the lowest illuminance (2300lumen/m2), but highest PpIX effective irradiance (37.0W/m2), and ultimately the lowest effective fluence at depth (0.18W/cm2 at 500µm). The daylight source had values of (outdoor | indoor) illuminance of (49,200 | 37,800 lumen/m2), effective irradiance of (19.2 | 10.7W/m2), and effective fluence of (1.50 | 1.08W/m2 at 500µm). The effective fluence and dose at depth facilitated the comparison of treatment regimens, for example, calculating an equivalent dose for a 2 hr indoor daylight treatment and a 10min red-light treatment for the 300-1000μm depth range. The consideration of PpIX-effective fluence at varying depths is necessary to provide adequate comparisons of the delivered dose from PDT light sources. Methods for calculating radiometric fluence and delivered dose at depth were introduced, with open source MATLAB code, to help overcome the limitations of commonly used photometric and irradiance-based reporting.

Polymer photosensitizing systems containing porphyrins, dinitrosyl iron complexes, and sodium alginate in the generation of singlet oxygen

The activity of photosensitizing systems based on water-soluble photoditazine (PDZ) and hydrophobic fluorinated tetraphenylporphyrin (TPPF20) solubilized polyvinylpyrrolidone (PVP) (in the case PDZ) and pluronic F127 (in the case TPPF20) was studied in a model reaction of tryptophan (Trp) photooxidation. We also studied the effect of dinitrosyl iron complex (DNIC) and sodium alginate (SA) polysaccharide on the photosensitizing activity of both PDZ in the presence of PVP and TPPF20 solubilized with pluronic F127 in a model reaction of Trp photooxidation. It was shown that TPPF20 solubilized with pluronic F127 exhibits high photocatalytic activity in the presence of both DNIC and SA. It was also shown that PVP is able to prevent the damaging effect exerted by active NO radicals produced during the photodecomposition of DNIC on PDZ molecules. Moreover, it was demonstrated that SA does not influence the photocatalytic activity of PDZ in the presence and absence of PVP. Using the dynamic light scattering method, it was found that SA macromolecules in the presence of PVP are capable of self-association, which, due to the ‘excluded volume’ effect, can cause a slight increase in the rate of photocatalytic reaction. The effectiveness of using PDZ in combination with PVP in the presence of SA and DNIC as a photosensitizer in antimicrobial photodynamic therapy was studied via in vivo experiments on a model of a full-layer planar wound in laboratory rats. Morphological studies have shown that under photodynamic action on wounds, the use of these systems (compared to photoexcitation of an aqueous solution of the initial PDZ) stimulates the transition of the inflammatory phase to the reparative (proliferative) phase. In addition, the process of cleansing wounds from microflora and devitalized tissues is accelerated, the disturbed microcirculation is restored, the proliferation of fibroblasts and blood vessels, and collagen synthesis are accelerated. It is suggested that the PDZ-PVP-SA-DNIC systems can be used in PDT procedures for the treatment of inflammatory diseases of the skin and soft tissues.

Ιnclusion Complexes of Magnesium Phthalocyanine with Cyclodextrins as Potential Photosensitizing Agents.

In this work, the preparation of inclusion complexes, (ICs) using magnesium phthalocyanine (MgPc) and various cyclodextrins (β-CD, γ-CD, HP-β-CD, Me-β-CD), using the kneading method is presented. Dynamic light scattering (DLS) indicated that the particles in dispersion possessed mean size values between 564 to 748 nm. The structural characterization of the ICs by infrared spectroscopy (FT-IR) and nuclear magnetic resonance (NMR) spectroscopy provides evidence of the formation of the ICs. The release study of the MgPc from the different complexes was conducted at pH 7.4 and 37 °C, and indicated that a rapid release ("burst effect") of ~70% of the phthalocyanine occurred in the first 20 min. The kinetic model that best describes the release profile is the Korsmeyer-Peppas. The photodynamic therapy studies against the squamous carcinoma A431 cell line indicated a potent photosensitizing activity of MgPc (33% cell viability after irradiation for 3 min with 18 mW/cm2), while the ICs also presented significant activity. Among the different ICs, the γ-CD-MgPc IC exhibited the highest photokilling capacity under the same conditions (cell viability 26%). Finally, intracellular localization studies indicated the enhanced cellular uptake of MgPc after incubation of the cells with the γ-CD-MgPc complex for 4 h compared to MgPc in its free form.

Enhancing the photosensitizing activity of natural flavins: Tuning the heavy-atom effect in the isoalloxazine series

Structure-photosensitizing activity relationships for a series of flavin analogues were investigated with the final goal of identifying the most potent photosensitizer in these series. The main structural modifications involved the introduction of various halogen atoms in C7- and/or C8-positions on the isoalloxazine ring. These compounds were synthesized by reacting judiciously-functionalized anilines with alloxan. The SAR trends showed that the photosensitizing activity increased with the size of the halogen atoms, confirming the importance of the heavy-atom effect on the photosensitizer’s activity. The halogens in C8 were more active than the di-substituted halogens, which in turn were more active than the C7-substituted equivalents. However, even if the photosensitizing activity is slightly less important for the 7- compared to the 8-substituted derivatives, the 7-haloisoalloxazines are promising photosensitizers, as they present a better cellular toxicity profile than the 8-substituted analoges. The photosensitizing activity perfectly correlated with the determined fluorescence for the same compounds. Except for the dihalogeno derivatives, all the compounds were not toxic up to a 50 μM range.

GM-CSF augmented the photothermal immunotherapeutic outcome of self-driving gold nanoparticles against a mouse CT-26 colon tumor model

BackgroundHypoxia is a frequent characteristic observed in solid tumors and is strongly associated with tumor metastasis, angiogenesis, and drug resistance. While the vasculature of hypoxic tumor tissues poses obstacles to the efficient administration of conventional drugs, it may prove advantageous in sustaining hyperthermia. Photothermal therapy (PTT) offers a promising treatment strategy that utilizes the activation of photosensitizers to produce heat, thus facilitating the selective ablation of tumor tissues.MethodTo enhance the accumulation of photothermal agents in tumor tissue and improve the effectiveness of PTT, we developed a self-propelled hybrid called Bif@PAu-NPs. This hybrid consists of polydopamine (PDA)-coated gold nanoparticles (Au-NPs) loaded onto the anaerobic Bifidobacterium infantis (Bif).ResultsThe Bif@PAu-NPs actively aggregated at the tumor site because the ability of Bif can target hypoxic regions, and PAu-NPs achieved precise PTT due to their high photothermal conversion efficiency (η = 67.8%). The tumor tissues were ablated by PTT, resulting in the release of antigens through immunogenic cell death (ICD), which stimulates an immune response. The inclusion of GM-CSF enhanced the immune response by recruiting dendritic cells and initiating long-term anti-tumor immunity.ConclusionThe Bif@PAu-NPs hybrid effectively suppressed the growth of both primary tumors and re-challenged tumors. The utilization Bif@PAu-NPs in conjunction with GM-SCF exhibits great potential as a photothermal-immunotherapeutic strategy for precisely treating solid tumors.Graphical In this study, the bacterial Bif@PAu-NPs biohybrid is exploited the self-driving ability of anaerobic Bifidobacterium infantis to deliver polydopamine-modified gold nanoparticles to hypoxic region of tumor. Under irradiation with 808 nm NIR laser, the hybrid exerts precise photothermal therapy to stimulate the immune response, which is further enhanced by GM-CSF, leading to recruitment of dendritic cells and initiation of a long-term anti-tumor immunity remember to prevent tumor recurrence.

Machine‐Learning Classification for the Prediction of Catalytic Activity of Organic Photosensitizers in the Nickel(II)‐Salt‐Induced Synthesis of Phenols

AbstractCatalytic systems using a small amount of organic photosensitizer for the activation of an inorganic (on‐demand ligand‐free) nickel(II) salt represent a cost‐effective method for cross‐coupling reactions, while C(sp2)−O bond formation remains less developed. Herein, we report a strategy for the synthesis of phenols with a nickel(II) salt and an organic photosensitizer, which was identified via an investigation into the catalytic activity of 60 organic photosensitizers consisting of various electron donor and acceptor moieties. To examine the effect of multiple intractable parameters on the catalytic activity of photosensitizers, machine‐learning (ML) models were developed, wherein we embedded descriptors representing their physical and structural properties, which were obtained from DFT calculations and RDKit, respectively. The study clarified that integrating both DFT‐ and RDKit‐derived descriptors in ML models balances higher “precision” and “recall” across a wide range of search space relative to using only one of the two descriptor sets.

Machine-Learning Classification for the Prediction of Catalytic Activity of Organic Photosensitizers in the Nickel(II)-Salt-Induced Synthesis of Phenols.

Catalytic systems using a small amount of organic photosensitizer for the activation of an inorganic (on-demand ligand-free) nickel(II) salt represent a cost-effective method for cross-coupling reactions, while C(sp2 )-O bond formation remains less developed. Herein, we report a strategy for the synthesis of phenols with a nickel(II) salt and an organic photosensitizer, which was identified via an investigation into the catalytic activity of 60 organic photosensitizers consisting of various electron donor and acceptor moieties. To examine the effect of multiple intractable parameters on the catalytic activity of photosensitizers, machine-learning (ML) models were developed, wherein we embedded descriptors representing their physical and structural properties, which were obtained from DFT calculations and RDKit, respectively. The study clarified that integrating both DFT- and RDKit-derived descriptors in ML models balances higher "precision" and "recall" across a wide range of search space relative to using only one of the two descriptor sets.

Added Value of Scintillating Element in Cerenkov-Induced Photodynamic Therapy.

Cerenkov-induced photodynamic therapy (CR-PDT) with the use of Gallium-68 (68Ga) as an unsealed radioactive source has been proposed as an alternative strategy to X-ray-induced photodynamic therapy (X-PDT). This new strategy still aims to produce a photodynamic effect with the use of nanoparticles, namely, AGuIX. Recently, we replaced Gd from the AGuIX@ platform with Terbium (Tb) as a nanoscintillator and added 5-(4-carboxyphenyl succinimide ester)-10,15,20-triphenylporphyrin (P1) as a photosensitizer (referred to as AGuIX@Tb-P1). Although Cerenkov luminescence from 68Ga positrons is involved in nanoscintillator and photosensitizer activation, the cytotoxic effect obtained by PDT remains controversial. Herein, we tested whether free 68Ga could substitute X-rays of X-PDT to obtain a cytotoxic phototherapeutic effect. Results were compared with those obtained with AGuIX@Gd-P1 nanoparticles. We showed, by Monte Carlo simulations, the contribution of Tb scintillation in P1 activation by an energy transfer between Tb and P1 after Cerenkov radiation, compared to the Gd-based nanoparticles. We confirmed the involvement of the type II PDT reaction during 68Ga-mediated Cerenkov luminescence, id est, the transfer of photon to AGuIX@Tb-P1 which, in turn, generated P1-mediated singlet oxygen. The effect of 68Ga on cell survival was studied by clonogenic assays using human glioblastoma U-251 MG cells. Exposure of pre-treated cells with AGuIX@Tb-P1 to 68Ga resulted in the decrease in cell clone formation, unlike AGuIX@Gd-P1. We conclude that CR-PDT could be an alternative of X-PDT.

Effect of Solubilizing Group on the Antibacterial Activity of Heptamethine Cyanine Photosensitizers.

Antibiotic resistance of pathogenic bacteria dictates the development of novel treatment modalities such as antimicrobial photodynamic therapy (APDT) utilizing organic dyes termed photosensitizers that exhibit a high cytotoxicity upon light irradiation. Most of the clinically approved photosensitizers are porphyrins that are poorly excitable in the therapeutic near-IR spectral range. In contrast, cyanine dyes function well in the near-IR region, but their phototoxicity, in general, is very low. The introduction of iodine atoms in the cyanine molecules was recently demonstrated to greatly increase their phototoxicity. Herein, we synthesized a series of the new iodinated heptamethine cyanine dyes (ICy7) containing various solubilizing moieties, i.e., negatively charged carboxylic (ICy7COOH) and sulfonic (ICy7SO3H) groups, positively charged triphenylphosphonium (ICy7PPh3), triethylammonium (ICy7NEt3) and amino (ICy7NH2) groups, and neutral amide (ICy7CONHPr) group. The effect of these substituents on the photodynamic eradication of Gram-positive (S. aureus) and Gram-negative (E. coli and P. aeruginosa) pathogens was studied. Cyanine dyes containing the amide and triphenylphosphonium groups were found to be the most efficient for eradication of the investigated bacteria. These dyes are effective at low concentrations of 0.05 µM (33 J/cm2) for S. aureus, 50 µM (200 J/cm2) for E. coli, and 5 µM (100 J/cm2) for P. aeruginosa and considered, therefore, promising photosensitizers for APDT applications. The innovation of the new photosensitizers consisted of a combination of the heavy-atom effect that increases singlet oxygen generation with the solubilizing group's effect improving cell uptake, and with effective near-IR excitation. Such a combination helped to noticeably increase the APDT efficacy and should pave the way for the development of more advanced photosensitizers for clinical use.

Potentialities of photoactivated disinfection in dentistry

Infection control is an essential part of dental practice. Oral antiseptics should be highly effective against the most common oral pathogens without causing microbial resistance, biocompatible with the human tissues with no interaction with fillings materials. Photoactivated disinfection (PAD) is based on activation of photosensitizers - specific substances releasing active oxygen forms after absorption of the light. The active oxygen forms destroy bacterial cell structures without affecting human cells. The overwhelming majority of Russian and international researchers have reported high effectiveness of PAD in periodontics, implantology and endodontics, whereas the use of PAD in caries treatment and prevention is not so fully understood yet. Earlier studies have demonstrated high sensitivity of cariogenic bacteria to PAD, suggesting it as an additional minimally invasive caries therapy improving treatment effectiveness. PAD spares dental tissues without reduction in the effectiveness of disinfection. It is particularly important in treatment of deep carious lesions and disinfection of thin dentine layer near the pulp. Effectiveness of PAD in caries treatment has been demonstrated for both permanent and deciduous dentition. PAD doesn't affect bond strength to fillings, improves plasticity of dental pulp and dental hard tissues mineralization in children. Effective control of a wide range of bacteria without causing resistance makes PAD a prospective method of treatment and prevention of caries.

An activatable photosensitizer for discriminative imaging and elimination of Gram-positive bacteria

• An activatable photosensitizer DPBO based on dibenzylideneacetone scaffold was prepared. • The emission and 1 O 2 generation of DPBO can be activated once targeting at bacteria. • DPBO can selectively discriminate and eliminate gram-positive bacteria at a low concentration of 0.25 µM in vitro . • DPBO can accelerate the healing rate of S. aureus infected wound in vivo . Photosensitizers with precise targeting and potent efficacy to infectious bacteria are highly demanded to tackle the threat of drug resistant bacteria. Here an antibacterial agent DPBO with activatable emission, effective 1 O 2 generation and bacterial selectivity was prepared. DPBO is able to selectively light up and synergistically kill Gram-positive bacteria including drug-resistant strains with a concentration as low as 0.25 µM in vitro and accelerate the healing rate of S. aureus infected wound in vivo . This study results provide a promising antibacterial candidate for developing new antibacterial materials.

A near-infrared and lysosome-targeted BODIPY photosensitizer for photodynamic and photothermal synergistic therapy.

Phototherapy is a promising approach for the treatment of cancers and other diseases. So far, many photosensitizers have been developed for photodynamic therapy (PDT) or photothermal therapy (PTT). However, it remains a challenge to develop a system for synergistic PDT and PTT with specific targeting and real-time fluorescence tracking. Herein, we designed a multifunctional BODIPY derivative, Lyso-BDP, for synergistic PDT and PTT against tumors. Lyso-BDP was composed of three parts: (1) the BODIPY fluorophore was selected as a theranostic core, (2) a morpholine group modified on meso-BODIPY served as a lysosome-targeting unit for enhancing the antitumor effect, and (3) N,N-diethyl-4-vinylaniline was attached to the BODIPY core to extend its wavelength to the near-infrared region. Finally, Lyso-BDP shows near-infrared absorption and emission, photosensitizing activity, lysosomal targeting, and synergistic PDT and PTT effects, and effectively kills cancer cells both in vitro and in vivo. Therefore, our study demonstrates that Lyso-BDP can serve as a promising photosensitizer in the therapy of cancer with potential clinical application prospects.

Atomic-scale observation of solvent reorganization influencing photoinduced structural dynamics in a copper complex photosensitizer.

Photochemical reactions in solution are governed by a complex interplay between transient intramolecular electronic and nuclear structural changes and accompanying solvent rearrangements. State-of-the-art time-resolved X-ray solution scattering has emerged in the last decade as a powerful technique to observe solute and solvent motions in real time. However, disentangling solute and solvent dynamics and how they mutually influence each other remains challenging. Here, we simultaneously measure femtosecond X-ray emission and scattering to track both the intramolecular and solvation structural dynamics following photoexcitation of a solvated copper photosensitizer. Quantitative analysis assisted by molecular dynamics simulations reveals a two-step ligand flattening strongly coupled to the solvent reorganization, which conventional optical methods could not discern. First, a ballistic flattening triggers coherent motions of surrounding acetonitrile molecules. In turn, the approach of acetonitrile molecules to the copper atom mediates the decay of intramolecular coherent vibrations and induces a further ligand flattening. These direct structural insights reveal that photoinduced solute and solvent motions can be intimately intertwined, explaining how the key initial steps of light harvesting are affected by the solvent on the atomic time and length scale. Ultimately, this work takes a step forward in understanding the microscopic mechanisms of the bidirectional influence between transient solvent reorganization and photoinduced solute structural dynamics.

MONOCATIONIC CHLORIN PHOTOSENSITIZER FOR EFFICIENT PHOTOINACTIVATION OF ANTIBIOTIC RESISTANT GRAM-NEGATIVE MICROORGANISMS

We propose a monocationic chlorin photosensitizer for antimicrobial photodynamic therapy of superficial localized infections. The antimicrobial activity of this specie towards planktonic forms of nosocomial anti-biotic resistant pathogens, viz. Pseudomonas aeruginosa, Enterobacter cloacae и Acinetobacter baumannii was studied and compared with the activity of the well-established photosensitizer “Fotoran e6”. Our results do indicate that monocationic chlorin provides efficient photoinactivation of all the three microorganisms and can be considered as a new agent for antimicrobial photodynamic therapy.

Axisymmetric bis-tridentate Ir(III) photoredox catalysts for anticancer phototherapy under hypoxia.

A novel axisymmetric bis-tridentate Ir(III) photocatalyst (Ir3) with synergetic type I/II photosensitization and photocatalytic activity was reported. Ir3 exhibited high photocytotoxicity toward drug-resistant cancer cells under normoxia and hypoxia. The photoactivated anticancer mechanism of Ir3 were investigated in detail. Overall, this new photo-redox catalyst can overcome hypoxia and drug resistance-related problems in clinical anticancer therapy.

Engineering of a GSH activatable photosensitizer for enhanced photodynamic therapy through disrupting redox homeostasis.

Although disrupted redox homeostasis has emerged as a promising approach for tumor therapy, most existing photosensitizers are not able to simultaneously improve the reactive oxygen species level and reduce the glutathione (GSH) level. Therefore, designing photosensitizers that can achieve these two aspects of this goal is still urgent and challenging. In this work, an organic activatable near-infrared (NIR) photosensitizer, CyI-S-diCF3, is developed for GSH depletion-assisted enhanced photodynamic therapy. CyI-S-diCF3, composed of an iodinated heptamethine cyanine skeleton linked with a recognition unit of 3,5-bis(trifluoromethyl)benzenethiol, can specifically react with GSH by nucleophilic substitution, resulting in intracellular GSH depletion and redox imbalance. Moreover, the activated photosensitizer can produce abundant singlet oxygen (1O2) under NIR light irradiation, further heightening the cellular oxidative stress. By this unique nature, CyI-S-diCF3 exhibits excellent toxicity to cancer cells, followed by inducing earlier apoptosis. Thus, our study may propose a new strategy to design an activatable photosensitizer for breaking the redox homeostasis in tumor cells.