Photoreactivity of polycyclic aromatic hydrocarbons (PAHs) and their mechanisms of phototoxicity against human immortalized keratinocytes (HaCaT).

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous organic compounds in the environment. They are produced by many anthropogenic sources of different origins and are known for their toxicity, carcinogenicity, and mutagenicity. Sixteen PAHs have been identified as Priority Pollutants by the US EPA, which are often associated with particulate matter, facilitating their dispersion through air and water. When human skin is exposed to PAHs, it might occur simultaneously with solar radiation, potentially leading to phototoxic effects. Phototoxic mechanisms involve the generation of singlet oxygen and reactive oxygen species, DNA damage under specific light wavelengths, and the formation of charge transfer complexes. Despite predictions of phototoxic properties for some PAHs, there remains a paucity of experimental data. This study examined the photoreactive and phototoxic properties of the 16 PAHs enlisted in the Priority Pollutants list. Examined PAHs efficiently photogenerated singlet oxygen and superoxide anion in simple solutions. Furthermore, singlet oxygen phosphorescence was detected in PAH-loaded HaCaT cells. Phototoxicity against human keratinocytes was evaluated using various assays. At 5 nM concentration, examined PAHs significantly reduced viability and mitochondrial membrane potential of HaCaT cells following the exposure to solar simulated light. Analyzed compounds induced a substantial peroxidation of cellular proteins after light treatment. The results revealed that a majority of the examined PAHs exhibited substantial reactive oxygen species photoproduction under UVA and violet-blue light, with their phototoxicity corresponding to their photoreactive properties. These findings improve our comprehension of the interactions between PAHs and human skin cells under environmental conditions, particularly when exposed to solar radiation.

Can l-ascorbic acid and trans-resveratrol protect HaCaT cells from fine particulate matter toxicity?

Continuous exposure of human skin to air pollution can result in a range of undesirable skin conditions. In our recent study, UV and visible light were found to increase cytotoxicity of fine particulate matter (PM2.5 ) against human keratinocytes. Since it is impossible to avoid exposure of human skin to PM2.5 , effective strategies are needed to reduce their damaging effects. l-ascorbic acid and resveratrol were tested as potential topical agents against pollution-related skin impairment. Although these agents were previously found to ameliorate PM-dependent damage, the effect of light and seasonal variation of particles were not previously studied. EPR spin-trapping, DPPH assay, and singlet oxygen phosphorescence were used to determine the scavenging activities of the antioxidants. MTT, JC-10 and iodometric assays were used to analyze the effect on PM2.5 -induced cytotoxicity, mitochondrial damage and oxidation of lipids. Live-cell imaging was employed to examine wound-healing properties of cells. Light-induced, PM2.5 -mediated oxidative damage was examined by immunofluorescent staining. Both antioxidants effectively scavenged free radicals and singlet oxygen produced by PM2.5 , reduced cell death and prevented oxidative damage to HaCaT cells. l-ascorbic acid and resveratrol, especially when applied in combination, can protect HaCaT cells against the dark and light induced toxicity of PM2.5 .

Astaxanthin protects human ARPE-19 retinal pigment epithelium cells from blue light-induced phototoxicity by scavenging singlet oxygen.

Age-related macular degeneration (AMD) is one of an increasing number of diseases that causes irreversible impairment and loss of vision in the elderly. AMD occurs by oxidative stress-mediated apoptosis of retinal pigment epithelium cells. The onset of AMD may be positively correlated with the exposure to blue light. We screened food-derived carotenoids for cytoprotective action against blue light irradiation using human ARPE-19 retinal pigment epithelium cells. This study revealed that blue light irradiation triggered apoptosis and oxidative stress in all-trans-retinal (atRAL)-exposed ARPE-19 cells by generating singlet oxygen (1O2), leading to significant cell death. We found that astaxanthin, a potent anti-oxidative xanthophyll abundant in several marine organisms including microalgae, salmon, and shrimp, significantly suppresses blue light-induced apoptotic cell death of atRAL-exposed ARPE-19 cells by scavenging 1O2. Mechanistic studies using the blue-light irradiated cells also demonstrated that the cytoprotective effects of astaxanthin can be attributed to scavenging of 1O2 directly. Our results suggest the potential value of astaxanthin as a dietary strategy to prevent blue light-induced retinal degeneration including AMD.

KEY POLICY HIGHLIGHTSBlue light irradiation triggered apoptosis and oxidative stress in all-trans-retinal (atRAL)-exposed human ARPE-19 retinal pigment epithelium cells by generating singlet oxygen (¹O₂), leading to significant cell death.Astaxanthin, a potent anti-oxidative xanthophyll abundant in several marine organisms including microalgae, salmon, and shrimp, significantly suppresses blue light-induced cell death of atRAL-exposed ARPE-19 cells.Astaxanthin inhibited apoptosis and oxidative stress induced by blue light by directly scavenging ¹O₂.

Antimicrobial Photodynamic Effect of Cross-Kingdom Microorganisms with Toluidine Blue O and Potassium Iodide.

Streptococcus mutans (S. mutans) and Candida albicans (C. albicans) are prominent microbes associated with rapid and aggressive caries. In the present study, we investigated the antimicrobial efficacy, cytotoxicity, and mechanism of toluidine blue O (TBO)-mediated antimicrobial photodynamic therapy (aPDT) and potassium iodide (KI). The dependence of KI concentration, TBO concentration and light dose on the antimicrobial effect of aPDT plus KI was determined. The cytotoxicity of TBO-mediated aPDT plus KI was analyzed by cell counting kit-8 (CCK-8) assay. A singlet oxygen (1O2) probe test, time-resolved 1O2 detection, and a 1O2 quencher experiment were performed to evaluate the role of 1O2 during aPDT plus KI. The generation of iodine and hydrogen peroxide (H2O2) were analyzed by an iodine starch test and Amplex red assay. The anti-biofilm effect of TBO-mediated aPDT plus KI was also evaluated by counting forming unit (CFU) assay. KI could potentiate TBO-mediated aPDT against S. mutans and C. albicans in planktonic and biofilm states, which was safe for human dental pulp cells. 1O2 measurement showed that KI could quench 1O2 signals, implicating that 1O2 may act as a principal mediator to oxidize excess iodide ions to form iodine and H2O2. KI could highly potentiate TBO-mediated aPDT in eradicating S. mutans and C. albicans due to the synergistic effect of molecular iodine and H2O2.

Oral Nanomotor-Enabled Mucus Traverse and Tumor Penetration for Targeted Chemo-Sono-Immunotherapy against Colon Cancer.

The therapeutic outcomes of oral nanomedicines against colon cancer are heavily compromised by their lack of specific penetration into the internal tumor, favorable anti-tumor activity, and activation of anti-tumor immunity. Herein, hydrogen peroxide (H2 O2 )/ultrasound (US)-driven mesoporous manganese oxide (MnOx )-based nanomotors are constructed by loading mitochondrial sonosensitizers into their mesoporous channels and orderly dual-functionalizing their surface with silk fibroin and chondroitin sulfate. The locomotory activities and tumor-targeting capacities of the resultant nanomotors (CS-ID@NMs) are greatly improved in the presence of H2 O2 and US irradiation, inducing efficient mucus-traversing and deep tumor penetration. The excess H2 O2 in the tumor microenvironment (TME) is decomposed into hydroxyl radicals and oxygen by an Mn2+ -mediated Fenton-like reaction, and the produced oxygen participates in sonodynamic therapy (SDT), yielding abundant singlet oxygen. The combined Mn2+ -mediated chemodynamic therapy and SDT cause effective ferropotosis of tumor cells and accelerate the release of tumor antigens. Importantly, animal experiments reveal that the treatment of combining oral hydrogel (chitosan/alginate)-embedding CS-ID@NMs and immune checkpoint inhibitors can simultaneously suppress the growth of primary and distal tumors through direct killing, reversion of immunosuppressive TME, and potentiation of systemic anti-tumor immunity, demonstrating that the CS-ID@NM-based platform is a robust oral system for synergistic treatment of colon cancer.

Biomimetic Cascade Polymer Nanoreactors for Starvation and Photodynamic Cancer Therapy.

The selective disruption of nutritional supplements and the metabolic routes of cancer cells offer a promising opportunity for more efficient cancer therapeutics. Herein, a biomimetic cascade polymer nanoreactor (GOx/CAT-NC) was fabricated by encapsulating glucose oxidase (GOx) and catalase (CAT) in a porphyrin polymer nanocapsule for combined starvation and photodynamic anticancer therapy. Internalized by cancer cells, the GOx/CAT-NCs facilitate microenvironmental oxidation by catalyzing endogenous H2O2 to form O2, thereby accelerating intracellular glucose catabolism and enhancing cytotoxic singlet oxygen (1O2) production with infrared irradiation. The GOx/CAT-NCs have demonstrated synergistic advantages in long-term starvation therapy and powerful photodynamic therapy (PDT) in cancer treatment, which inhibits tumor cells at more than twice the rate of starvation therapy alone. The biomimetic polymer nanoreactor will further contribute to the advancement of complementary modes of spatiotemporal control of cancer therapy.

Photodynamic Inactivation of Legionella pneumophila Biofilm Formation by Cationic Tetra- and Tripyridylporphyrins in Waters of Different Hardness.

The bacterium Legionella pneumophila is still one of the probable causes of waterborne diseases, causing serious respiratory illnesses. In the aquatic systems, L. pneumophila exists inside free-living amoebae or can form biofilms. Currently developed disinfection methods are not sufficient for complete eradication of L. pneumophila biofilms in water systems of interest. Photodynamic inactivation (PDI) is a method that results in an antimicrobial effect by using a combination of light and a photosensitizer (PS). In this work, the effect of PDI in waters of natural origin and of different hardness, as a treatment against L. pneumophila biofilm, was investigated. Three cationic tripyridylporphyrins, which were previously described as efficient agents against L. pneumophila alone, were used as PSs. We studied how differences in water hardness affect the PSs' stability, the production of singlet oxygen, and the PDI activity on L. pneumophila adhesion and biofilm formation and in biofilm destruction. Amphiphilic porphyrin showed a stronger tendency for aggregation in hard and soft water, but its production of singlet oxygen was higher in comparison to tri- and tetracationic hydrophilic porphyrins that were stable in all water samples. All three studied porphyrins were shown to be effective as PDI agents against the adhesion of the L. pneumophila to polystyrene, against biofilm formation, and in the destruction of the formed biofilm, in their micromolar concentrations. However, a higher number of dissolved ions, i.e., water hardness, generally reduced somewhat the PDI activity of all the porphyrins at all tested biofilm growth stages.

The Polarity of Fullerene C60 Derivatives for Enhanced Photodynamic Inactivation.

In this article, four novel fulleropyrrolidines derivatives were synthesized to study how the effect of polarity and positive charge distribution can influence the efficacy of photodynamic inactivation treatments to kill bacteria. The design of the photosensitizers was based on DFT calculations that allowed us to estimate the dipolar moment of the molecules. Neutral compounds bearing N-methyl bis-acetoxy-ethyl (1) and bis-hydroxyethyl (2) amine were the starting material to obtain the dicationic analogs N,N-dimethyl bis-methoxyethyl (3), and bis-acetoxy-ethyl) (4) methylammonio. As expected from fullerene C60 derivatives, compounds 1-4 absorb in the UV region, with a peak at 430 nm, a broader range of absorption up to 710 nm, and exhibit weak fluorescence emission in toluene and reverse micelles. In the biomimetic AOT micellar system, the highest singlet oxygen photosensitization was found for compounds 1, followed by 3, 2, and 4. Whereas 4 was the most effective reducing nitro blue tetrazolium in the presence of ß-NADH. The influence of type I and type II mechanism on the photodynamic activity of compounds 3 and 4 was further examined in the presence of L-tryptophan and two reactive oxygen species scavengers. In vitro experiments indicated that the compounds with the highest dipolar moments, 3 (37.19 D) and 4 (38.46 D), inactivated methicillin-resistant Staphylococcus aureus and Escherichia coli bacteria using an energy dose <2.4 J cm-2 . No inactivation was observed for the neutral analogs with the lowest dipolar moments. These findings help to optimize sensitizer structures to improve photodynamic inactivation.

Natural photosensitizers from Tripterygium wilfordii and their antimicrobial photodynamic therapeutic effects in a Caenorhabditis elegans model.

Tripterygium wilfordii Hook. f. is a traditional medicinal plant and has long been used in East Asia to treat many diseases. However, the extract and active components have never been investigated as potential photosensitizers for photodynamic treatment to kill pathogenic microorganisms. Here, the antimicrobial photodynamic treatment (APDT) effects of the extract, fractions, and compounds of T. wilfordii were evaluated in vitro and in vivo. Ethanolic extract (TWE) and the photosensitizer-enriched fraction (TW-F5) were prepared from dried T. wilfordii. Six active compounds were isolated from TW-F5 by semipreparative high-performance liquid chromatography, and their chemical structures were characterized through spectroscopic and spectrometric analysis. The singlet oxygen from extracts, fractions, and compounds was measured by using the imidazole-N,N-dimethyl-4-nitrosoaniline method. These extracts, fractions, and compounds were used as photosensitizers for the inactivation of bacteria and fungi by red light at 660 nm. The in vitro APDT effects were also evaluated in the model animal Caenorhabditis elegans. APDT with TWE showed effective antimicrobial activity against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), and Candida albicans. TW-F5, consisting of six pheophorbide compounds, also showed strong APDT activity. The photosensitizers were taken up into the bacterial cells and induced intracellular ROS production by APDT. TWE and TW-F5 also induced a strong APDT effect in vitro against skin pathogens, including Staphylococcus epidermidis and Streptococcus pyogenes. We evaluated the APDT effects of TWE and TW-F5 in C. elegans infected with various pathogens and found that PDT effectively controlled pathogenic bacteria without strong side effects. APDT reversed the growth retardation of worms induced by pathogen infection and decreased the viable pathogenic bacterial numbers associated with C. elegans. Finally, APDT with TWE increased the survivability of C. elegans infected with S. pyogenes. In summary, TWE and TW-F5 were found to be effective antimicrobial photosensitizers in PDT.

Chlorin e6-1,3-diphenylisobenzofuran polymer hybrid nanoparticles for singlet oxygen-detection photodynamic abaltion.

A dual-functional nanosysterm is developed by means of Chlorin e6 (Ce6) as photosensitizer and 1,3-Diphenylisobenzofuran (DPBF) as fluorescent singlet oxygen (1O2) probe. Under 660 nm laser irradiation, Ce6 exhibites efficient 1O2 generation, and subsequently the production of 1O2 is assessed by the ratiometric fluorescence of PFO and DPBF under one-photon and two-photon excitation mode. The nanoparticles with excellent biocompatibility can be internalized into Hela cells and applied for tumor treatment. For intracellular PDT, the nanoparticles perform a high phototoxicity, while the PDT proccess can be evaluated in time by monitoring fluorescence signals of DPBF. This theranostic nanosysterm provides a facile strategy to fabricate 1O2-detection PDT, which can realize accurate and efficient photodynamic therapy based on singlet oxygen detection.

A photoactivatable antibody-Chlorin e6 conjugate enabling singlet oxygen production for tumor-targeting photodynamic therapy.

Photodynamic therapy is a new technology for disease diagnosis and treatment in modern medical clinics. The main advantages of photodynamic therapy are low toxicity and side effects, a wide range of applications, no drug resistance, and no obvious trauma in the treatment process. However, to achieve effective photodynamic therapy, new photosensitizer carriers need to be constructed, which can selectively deliver photosensitizers into tumor tissues. In this work, a photoactivatable antibody-Chlorin e6 conjugate with a dual-function to target tumor tissue and realize cancer photodynamic therapy is constructed. Bothin vitroandin vivoexperiments indicate that the antibody-Chlorin e6 conjugate has the ability to target tumors rapidly and efficiently, and has the ability to generate reactive oxygen species and kill tumor cells. Overall, this photoactivable antibody-Chlorin e6 conjugate may provide a promising strategy to address the current challenges of cancer photodynamic therapy.

Self-Driven Reactive Oxygen Species Generation via Interfacial Oxygen Vacancies on Carbon-Coated TiO2-x with Versatile Applications.

The effective activation and utilization of O2 have always been the focus of scientists because of its wide applications in catalysis, organic synthesis, life and medical science. Here, a novel method for activating O2 spontaneously via interfacial oxygen vacancies on carbon-coated TiO2-x to generate reactive oxygen species (ROS) with versatile applications is reported. The interfacial oxygen vacancies can be stabilized by the carbon layer and hold its intrinsic properties for spontaneous oxygen activation without light irradiation, while common surface oxygen vacancies on TiO2-x are always consumed by the capture of H2O to form the surface hydroxyls. Thus, O2 absorbed at the interface of carbon and TiO2-x can be directly activated into singlet oxygen (1O2) or superoxide radicals (·O2-), confirmed both experimentally and theoretically. These reactive oxygen species exhibit excellent performance in oxidation reactions and inhibition of MCF-7 cancer cells, providing new insight into the effective utilization of O2 via oxygen vacancies on metal oxides.

Staphylococcus aureus biofilm eradication by the synergistic effect exerted by PEG-coated silicon dots immobilized in silica films and light irradiation.

Immobilization of PEG-covered silicon dots, PEGSiDs, on glass substrates was performed following a simple strategy involving particle embedding by a sol-gel process forming a silica film on glass slides. The obtained films, denoted as fSiO x -PEGSiD, constitute a water-wettable, strongly supported, photoluminescent glass coating. The films showed high capacity for photosensitizing singlet oxygen (1O2) in the UVA when immersed in water. Staphylococcus aureus colonies formed on fSiO x -PEGSiDs modified glasses revealed the inhibition of bacterial adhesion and bacterial growth leading to the formation of loosely-packed and smaller S. aureus colonies. Upon 350 nm light irradiation of the biofilmed fSiO x -PEGSiDs -modified glasses, S. aureus growth was inhibited and bacteria killed reducing the number of living bacteria by three orders of magnitude. Eradication of attached bacteria was achieved by the synergistic effect exerted by a less adherent fSiO x -PEGSiDs surface that inhibits biofilm formation and the ability of the surface to photosensitize 1O2 to kill bacteria.

Hollow Bimetallic Complex Nanoparticles for Trimodality Imaging and Photodynamic Therapy In Vivo.

Hollow nanoparticles have received an enormous amount of attention in the field of nanomedicine. Herein, water-soluble hollow bimetallic complex nanoparticles, holmium(III)/iridium(III) bimetallic complex nanoparticles (Ir-Ho HNPs), were fabricated via a coordination assembly. Owing to the special metal-to-ligand charge transfer (MLCT) and the heavy-atom effect of Ir(III) in an iridium complex, Ir-Ho HNPs exhibited an intense phosphorescence and the generation of singlet oxygen (1O2). With the long electron relaxation time and high magnetic moment of Ho(III), Ir-Ho HNPs presented a high longitudinal relaxivity (r2) value (160.0 mM-1 s-1at 7.0 T). Their unique hollow structure resulted in their strong and stable ultrasound signal in an aqueous solution. As a proof of concept, Ir-Ho HNPs have been developed for the phosphorescence imaging and photodynamic therapy for living cells, ultrasound imaging, and high-field magnetic resonance imaging in vivo. Our work opened up an avenue for novel application of an iridium complex in cancer theranostics.

Anti- and pro-oxidative mechanisms comparing the macular carotenoids zeaxanthin and lutein with other dietary carotenoids - a singlet oxygen, free-radical in vitro and ex vivo study.

The interactions of dietary carotenoids, and particularly the xanthophylls in the macula, with singlet oxygen and three different oxy-radicals, (hydroxyl radical, nitrogen dioxide and the superoxide radical anion) are compared using pulsed laser and γ-techniques. The results give possible molecular mechanisms for the switch from anti-oxidant (protection) by carotenoids to pro-oxidant (damage) by carotenoids. The participation of oxygen in radical mechanisms in the presence of different carotenoids is compared for the different radicals. It is shown that the mechanistic role of oxygen differs very significantly for anti-/pro-oxidation by hydroxyl radicals when compared to nitrogen dioxide. Lutein was found to be an extremely good cell protector against hydroxyl radicals at all oxygen concentrations, including under physiological conditions.

Engineering of fluorescent or photoactive Trojan probes for detection and eradication of ß-Amyloids.

Trojan horse technology institutes a potentially promising strategy to bring together a diagnostic or cell-based drug design and a delivery platform. It provides the opportunity to re-engineer a novel multimodal, neurovascular detection probe, or medicine to fuse with blood-brain barrier (BBB) molecular Trojan horse. In Alzheimer's disease (AD) this could allow the targeted delivery of detection or therapeutic probes across the BBB to the sites of plaques and tangles development to image or decrease amyloid load, enhance perivascular Aß clearance, and improve cerebral blood flow, owing principally to the significantly improved cerebral permeation. A Trojan horse can also be equipped with photosensitizers, nanoparticles, quantum dots, or fluorescent molecules to function as multiple targeting theranostic compounds that could be activated following changes in disease-specific processes of the diseased tissue such as pH and protease activity, or exogenous stimuli such as, light. This concept review theorizes the use of receptor-mediated transport-based platforms to transform such novel ideas to engineer systemic and smart Trojan detection or therapeutic probes to advance the neurodegenerative field.

Fluorinated-functionalized hyaluronic acid nanoparticles for enhanced photodynamic therapy of ocular choroidal melanoma by ameliorating hypoxia.

Photodynamic therapy (PDT) is a method for killing cancer cells by employing reactive singlet oxygen (1O2). However, the inherent hypoxia and oxygen consumption in tumors during PDT lead to a deficient oxygen supply, which in turn hinder the photodynamic efficacy. To overcome this issue, fluorinated-functionalized polysaccharide-based nanocomplexes were prepared by anchoring perfluorocarbons (PFCs) and pyropheophorbide a (Ppa) onto the polymer chains of hyaluronic acid (HA) to deliver O2 in hypoxia area. These amphiphilic conjugates can self-assemble into micelles and its application in PDT is evaluated. Due to the high oxygen affinity of perfluorocarbon segments, and the tumor-targeting nature of HA, the photodynamic effect of the oxygen self-carrying micelles is remarkably enhanced, which is confirmed by increased generation of 1O2 and elevated phototoxicity in vitro and in vivo. These results emphasize the promising potential of polysaccharide-based nanocomplexes for enhanced PDT of Ocular Choroidal Melanoma.

Iron Magnetic Nanoparticle-Induced ROS Generation from Catechol-Containing Microgel for Environmental and Biomedical Applications.

Reactive oxygen species (ROS) can degrade organic compounds and function as a broad-spectrum disinfectant. Here, dopamine methacrylamide (DMA) was used to prepare catechol-containing microgels, which can release ROS via metal-catechol interaction. A combination of the microgel and iron magnetic nanoparticle (FeMNP) significantly reduced the concentration of four organic dyes (Alizarin Red S, Rhodamine B, Crystal Violet, and Malachite Green) and an antibiotic drug, ciprofloxacin, dissolved in solution. Degradation of dye occurred across a wide range of pH levels (pH 3-9). This simple combination was also antimicrobial against both Escherichia coli and Staphylococcus aureus. Electron paramagnetic resonance spectroscopy (EPR) results indicate that singlet oxygen was generated during the reaction between catechol and FeMNP at both pH 3 and 7.4, which was responsible for the degradation of organic compounds and bactericidal features of the microgel. Unlike autoxidation that only occurs at a neutral to basic pH, FeMNP-induced catechol oxidation generated singlet oxygen over a wide range of pH level. Additionally, catechol chelates heavy metal ions, resulting in their removal from solution and repurposed these metal ions for dye degradation. This multifunctional microgel can potentially be used for environmental applications for the removal of organic pollutants and heavy metal ions from wastewater, as well as reducing bacterial infection in biomedical applications.

Self-assembled single-atom nanozyme for enhanced photodynamic therapy treatment of tumor.

Hypoxia of solid tumor compromises the therapeutic outcome of photodynamic therapy (PDT) that relies on localized O2 molecules to produce highly cytotoxic singlet oxygen (1O2) species. Herein, we present a safe and versatile self-assembled PDT nanoagent, i.e., OxgeMCC-r single-atom enzyme (SAE), consisting of single-atom ruthenium as the active catalytic site anchored in a metal-organic framework Mn3[Co(CN)6]2 with encapsulated chlorin e6 (Ce6), which serves as a catalase-like nanozyme for oxygen generation. Coordination-driven self-assembly of organic linkers and metal ions in the presence of a biocompatible polymer generates a nanoscale network that adaptively encapsulates Ce6. The resulted OxgeMCC-r SAE possesses well-defined morphology, uniform size distribution and high loading capacity. When conducting the in situ O2 generation through the reaction between endogenous H2O2 and single-atom Ru species of OxgeMCC-r SAE, the hypoxia in tumor microenvironment is relieved. Our study demonstrates a promising self-assembled nanozyme with highly efficient single-atom catalytic sites for cancer treatment.

A dormant BODIPY-acrolein singlet oxygen photosensitizer intracellularly activated upon adduct formation with cysteine residues.

Here we report the activatable photosensitizer BromoAcroB, a brominated BODIPY dye incorporating a reactive acrolein warhead. The acrolein moiety serves as an intramolecular switch, deactivating the BODIPY dye in its singlet and triplet excited states via internal conversion. Thiolate addition to this moiety disables the intramolecular quenching mechanism restoring the photosensitizing properties of the parent dye, characterized by a quantum yield of singlet oxygen photosensitization of 0.69 ± 0.02. In cell cultures, and upon thiol adduct formation, BromoAcroB induced light-dependent cell death in MRC-5 and HeLa cell lines. Using fluorescence microscopy and upon measuring the low yet non-negligible emission of the activated compound, we show that the phototoxicity of the dormant photosensitizer correlated with the quantity of BromoAcroB adducts generated. BromoAcroB thus serves as a dormant photosensitizer sensitive to intracellular electrophile response. Our results highlight the effective control of a triplet state process by modulation of an unsaturated moiety on the BODIPY scaffold and underscore the mechanistic opportunities arising for controlled singlet oxygen production in cells specifically sensitive to electrophile stress.