Singlet Oxygen Generation Research Articles

The remediation performance and mechanism for tetracycline from groundwater using controlled release materials containing mesoporous MnOx with different morphology

Aiming at the effective remediation of antibiotic contaminants in groundwater, in-situ chemical oxidation (ISCO), using controlled release materials (CRMs) as an oxidant deliverer, has emerged as a promising technique due to their long-term effective pollutant removal performance. This study used different microstructures of mesoporous manganese oxide (MnOx) and sodium persulfate as active components to fabricate CRMs. Following that, a comparative study of tetracycline (TC) degradation and the formation of reactive oxygen species (ROS) by mesoporous MnOx powder and CRMs were conducted. The ROS formed during peroxodisulfate (PDS) activation by powder catalysts and CRMs differed, but MnOx powder catalysts and CRMs both had good reaction stoichiometric efficiency (RSE) for PDS, thus completely mineralizing TC. In PDS activation by mesoporous MnOx powder, oxygen vacancies (OVs) caused by defects in the catalysts contributed to the generation of singlet oxygen (1O2). The 1O2 and free radicals (·SO4- and ·OH) both worked as major ROS participating in TC degradation. Concerning the release of CRMs in static groundwater, the immobilization of catalysts inside CRMs made it difficult to release 1O2 in the solution, thus slowing the degradation of TC by CRMs containing MnOx(1) in static groundwater. In the TC remediation in dynamic groundwater, the water flowing slowly passed through the CRM layer, and TC molecules were trapped. Therefore, 1O2 degraded the trapped TC in the CRM layer in dynamic groundwater. Compared to TC, the toxicity of most intermediates during the TC degradation by CRMs has decreased in static and dynamic groundwater.

Mechanistic insights into the pH-driven radical transformation of the Fe(II)/nCP in groundwater remediation.

Calcium peroxide nanoparticles (nCP) as a versatile and safe solid H2O2 source, have attractedsignificant research interst for their application potential in groundwater remediation. Compared to the traditional Fenton system, the nCP-based Fenton-like system has a wider pH-working window for contaminants degradation. This results from the dominant radical transformation under different pH. Unlike the traditional Fenton system which is only effective in acid conditions with hydroxyl radical (•OH) as the main active species, the release of H2O2 and O2 from nCP provides multiple contaminants degradation pathways. In acidic environments, •OH and Fe(IV) predominate as the active species, facilitated by substantial H2O2 production which activates the Fenton reaction. In neutral or alkaline conditions, the production of H2O2 was dramatically decreased. While the O2 released from nCP can be catalyzed by Fe(II) to form superoxide radical (•O2-), which subsequently generate singlet oxygen (1O2). The formation pathway of •O2- was tracked by O18 isotope labeling experiment. The impact of the water matrix on radical generation in the Fe(II)/nCP Fenton-like system was also studied. This research deepens the understanding of the radical formation mechanisms in nCP-based Fenton-like system, offering insights to support their application in remediating contaminated groundwater.

Encapsulation of an Au25 Nanocluster inside a Porphyrin Nanoring Enhances Singlet Oxygen Generation and Photo‐Electrocatalytic CO2 Reduction

AbstractThe synthesis of molecular host–guest complexes with enhanced performance, relative to those of their components, is a central theme in supramolecular chemistry. Here we explore a host‐guest system consisting of an atomically precise gold nanocluster bound inside a zinc porphyrin nanoring. UV/Vis absorption and fluorescence titrations with different sized nanorings revealed strong binding between a pyridinethiol‐coated Au25 nanocluster and a nanoring consisting of six zinc porphyrin units, and complexation is confirmed by mass spectrometry. Formation of this assembly enhances the stability of the gold nanocluster. The host‐guest complex also exhibits remarkable activity and selectivity for photochemical CO2 to CO conversion and singlet oxygen generation.

Suppressing Effect of Flavonoid Compounds on Lipids Photooxidation of Sheep Red Blood Cells and Oleic Acid Photooxidation

ABSTRACTPhotosensitizers and pigments in raw meat such as porphyrins, riboflavin, and myoglobin after incorporation with light beam prompt the generation of singlet oxygen (1O2) from triplet oxygen (3O2) and cause oxidative rancidity of meat products. In this study, the results of photooxidation reactions of sheep erythrocyte (red blood cell) model as a model rich in hemoglobin and phospholipids bilayer, and oleic acid model were obtained by 1H NMR spectroscopy, TBARS assay, and iodometric titration. In both models, the rate of lipid photooxidation in the presence of hydroalcoholic extracts of Turmeric (Curcuma longa L.) and Cumin (Cuminum cyminum L.) as natural antioxidants, Butyl hydroxytoluene (BHT) as a synthetic antioxidant, and sodium azide (NaN3) as a well‐known 1O2 scavenger were decreased in the order of NaN3 > Turmeric > Cumin > BHT. It was proven that during the photooxidation process, there is a direct association between the amount of flavonoid compounds and 1O2 scavenging.

Liposomal Formulations of Novel BODIPY Dimers as Promising Photosensitizers for Antibacterial and Anticancer Treatment

Synthesis, photochemical properties, liposomal encapsulation, and in vitro photodynamic activity studies of novel BODIPY dimer connected at meso-meso positions and its brominated and iodinated analogs were described. UV-Vis measurements indicated that the dimeric structure of obtained BODIPYs did not significantly influence the positions of the absorption maxima. Emission properties and singlet oxygen generation studies revealed a strong heavy atom effect of brominated and iodinated BODIPY dimers, manifested by fluorescence intensity reduction and increased singlet oxygen generation ability compared to analog without halogen atoms. For the in vitro photodynamic activity studies, dimers were incorporated into two different types of liposomes: positively charged DOTAP:POPC and negatively charged POPG:POPC. The photoinactivation studies revealed high activity of brominated and iodinated dimers incorporated into DOTAP:POPC liposomes on both Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli. Anticancer studies on human breast adenocarcinoma MDA-MB-231 and human ovarian carcinoma A2780 cells revealed that DOTAP:POPC liposomes containing brominated and iodinated dimers were active even at low nanomolar concentrations. In addition, they were more active against MDA-MB-231 cells than A2780 cells, which is particularly important since the MDA-MB-231 cell line represents triple-negative breast cancer, which has limited therapeutic options.

Modulating Pore Wall Chemistry Empowers Sonodynamic Activity of Two‐Dimensional Covalent Organic Framework Heterojunctions for Pro‐Oxidative Nanotherapy

AbstractCovalent organic frameworks (COFs) have garnered growing interest in the field of biomedicine; however, their application in sonodynamic therapy remains underexplored due to limited understanding of their intrinsic activity and structure–property relationships. Here, we present a pore wall chemistry modulation strategy for empowering sonodynamic activity to two‐dimensional (2D) COF heterojunctions through in situ growth of COFs on bismuth oxycarbonate nanosheets (B NSs). Compared to the negligible sonodynamic effects observed in the pristine B NSs, the 2D heterojunction with vinyl‐decorated COF pore walls demonstrates a 3.6‐fold enhancement in sonocatalytic singlet oxygen generation. This performance also significantly outperforms that of isoreticular COFs functionalized with methoxy or non‐substituted groups. Mechanistic studies reveal that the vinyl groups in the B@COF (BC) heterojunction facilitate the separation and transfer of charge carriers while also enhancing the adsorption of oxygen molecules. Furthermore, peroxymonosulfate (PMS) loading into the porous COFs boosts the therapeutic efficacy of antitumor nanotherapy via sonocatalytic dual oxidative species generation. These findings underscore the critical role of pore wall chemistry in modulating the sonocatalytic properties of COFs, and advance the development of COF‐based sonosensitizers for pro‐oxidative applications.

Enhancing Phototoxicity in BODIPY-Perylene Charge Transfer Dyads by Combined Iodination and Mesylation.

The uptake and phototoxicity of a family of BODIPY-perylene charge transfer dyads are compared in live cancer and non-cancer cell lines to evaluate their performance in imaging and photodynamic therapy (PDT). The impact of iodination and mesylation of the meso position of the compounds on their optical properties, cell uptake and toxicity are compared. Notably, across all derivatives the probes were minimally dark toxic up to 50 μM, (the maximum concentration tested), but exhibited outstanding phototoxicity with nanomolar IC50 values and impressive phototoxic indices (PI, ratio of dark IC50 to light IC50), with best performance for the mesylated iodinated derivative MB2PI, which had a PI of >218 and >8.9 in MCF-7 cells and tumour spheroids respectively. This is significantly higher than non-iodinated analogue MB2P in MCF-7 cells with an observed PI of >109 and slightly higher than MB2PI in spheroids with a PI of >8. This compound also showed interesting emission spectral variation with localisation that responded to stimulation of inflammation. Additional studies confirmed efficient singlet oxygen generation by the BODIPYs, suggesting a Type II mechanism of phototoxicity. Overall, the data indicates that combining charge transfer and iodination is an effective strategy for enhancing phototherapeutic capacity of BODIPY PS.

Oxygen-Doped Porous Ultrathin Graphitic Carbon Nitride Nanosheets for Photocatalytic Hydrogen Evolution and Rhodamine B Degradation.

Graphite phase carbon nitride (g-C3N4) is a highly promising metal-free photocatalyst, but its low activity, due to limited quantum efficiency and small specific surface area, restricts its practical application. While exfoliating bulk crystals into porous thin-layer nanosheets and incorporating dopants have been shown to improve photocatalytic efficiency, these methods are typically complex, time-consuming, and costly processes. In this study, we developed a simple approach to synthesize oxygen-doped porous g-C3N4 (OCN) nanosheets. The resulting OCN exhibited significantly enhanced light absorption and visible-light photocatalytic activity compared to bulk g-C3N4 (BCN) and g-C3N4 (CN). The OCN achieved an impressive hydrogen evolution reaction (HER) rate of 8.02 mmol g-1 h-1, eight times greater than BCN, and demonstrated a high Rhodamine B (RhB) degradation rate of 97.3 % owing to the generation of abundant singlet oxygen. These improvements in photocatalytic performance are attributed to the narrow band gap and enhanced electron transfer properties, suggesting a promising route for the efficient design of g-C3N4-based photocatalysts.

Smart molecular designs and applications of activatable organic photosensitizers.

Photodynamic therapy (PDT) - which combines light, oxygen and photosensitizers (PS) to generate reactive oxygen species - has emerged as an effective approach for targeted ablation of pathogenic cells with reduced risk of inducing resistance. Some organic PS are now being applied for PDT in the clinic or undergoing evaluation in clinical trials. A limitation of the first-generation organic PS was their potential off-target toxicity. This shortcoming prompted the design of constructs that can be activated by the presence of specific biomolecules - from small biomolecules to large enzymes - in the target cells. Here, we review advances in the design and synthesis of activatable organic PS and their contribution to PDT in the past decade. Important areas of research include novel synthetic methodologies to engineer smart PS with tuneable singlet oxygen generation, their integration into larger constructs such as bioconjugates, and finally, representative examples of their translational potential as antimicrobial and anticancer therapies.

Anthracene-Based Endoperoxides as Self-Sensitized Singlet Oxygen Carriers for Hypoxic-Tumor Photodynamic Therapy.

Singlet oxygen is a crucial reactive oxygen species (ROS) in photodynamic therapy (PDT). However, the hypoxic tumor microenvironment limits the production of cytotoxic singlet oxygen through the light irradiation of PDT photosensitizers (PSs). This restriction poses a major challenge in improving the effectiveness of PDT. To overcome this challenge, researchers have explored the development of singlet oxygen carriers that can capture and release singlet oxygen in physiological conditions. Among these developments, anthracene-based endoperoxides, initially discovered almost 100 years ago, have shown the ability to generate singlet oxygen controllably under thermal or photo stimuli. Recent advancements have led to the development of a new class of self-sensitized anthracene-endoperoxides, with potential applications in enhancing PDT effects for hypoxic tumors. This review discusses the current research progress in utilizing self-sensitized anthracene-endoperoxides as singlet oxygen carriers for improved PDT. It covers anthracene-conjugated small organic molecules, metal-organic complexes, polymeric structures, and other self-sensitized nano-structures. The molecular structural designs, mechanisms, and characteristics of these systems will be discussed. This review aims to provide valuable insights for developing high-performance singlet oxygen carriers for hypoxic-tumor PDT.

Pd/UiO‐66(Zr)‐2OH as a High‐Performance Catalyst for Hydrogen‐Enhanced Fenton Oxidation of Trimethoprim

ABSTRACTA novel catalyst material named Pd/UiO‐66(Zr)‐2OH was successfully developed and applied in a hydrogen‐promoted Fenton system for the efficient catalytic oxidation of the widely used antibiotic trimethoprim (TMP). The UiO‐66(Zr)‐2OH, as the carrier of catalyst in this work, was synthesized through a solvothermal method. The Pd0 nanoparticle, as the active center of the catalyst, was loaded onto its surface by the “ship‐in‐a‐bottle” strategy. The results showed that the composite Pd/UiO‐66(Zr)‐2OH demonstrated excellent catalytic performance during the reaction, achieving over 97% of TMP removal efficiency within 180 min under optimal conditions under the condition of only trace of iron without adding H2O2. This may be attributed to the fact that the [H], as a clean and efficient reducing agent, can be utilized to accelerate the regeneration of Fe2+ in the Fenton reaction, as well as in the in‐situ regeneration of H2O2. The key parameters affecting the removal efficiency of TMP, including the initial pH and concentration of Fe2+, the dosage of the synthesized material, the flow rate of H2 and the stirring speed were investigated systematically. The Pd/UiO‐66(Zr)‐2OH exhibited high stability and reusability, maintaining over 82% of its initial degradation efficiency of TMP after six reaction cycles. The mechanistic insight revealed that the system primarily relied on the generation of hydroxyl radical (·OH) and singlet oxygen (1O2) for the degradation of TMP, which was verified through quenching experiments and electron spin resonance (ESR). The degradation pathway of TMP was elucidated by analyzing intermediates and the reduction in total organic carbon (TOC). This research offers novel conceptual insights into the evolution and application of advanced oxidation technologies, efficient degradation of emerging pollutants, and expansion of pathways for hydrogen resource utilization.

Artificial Light-Harvesting Systems with a Three-Step Sequential Energy Transfer Mechanism for Efficient Photocatalytic Minisci-Type Late-Stage Functionalization.

The natural process of photosynthesis involves a series of consecutive energy transfers, but achieving more steps of efficient energy transfer and photocatalytic organic conversion in artificial light-harvesting systems (ALHSs) continues to pose a significant challenge. In the present investigation, a range of ALHSs showcasing a sophisticated three-step energy transfer mechanism is designed, which are meticulously crafted using pillar[5]arene (WP[5]) and p-phenylenevinylene derivative (PPTPy), utilizing host-guest interactions as energy donors. Three distinct types of fluorescent dyes, namely Rhodamine B (RhB), Sulforhodamine 101 (SR101), and Cyanine 5 (Cy5), are employed as acceptors of energy. Starting from PPTPy-2WP[5], energy is sequentially transferred to RhB, SR101, and Cy5, successfully constructing a multi-step continuous energy transfer system with high energy transfer efficiency. More interestingly, as energy is progressively transferred, the efficiency of superoxide anion radical (O2 •-) generation gradually increased, while the efficiency of singlet oxygen (1O2) generation decreased, achieving the transformation from type II photosensitizer to type I photosensitizer. Furthermore, in order to fully utilize the energy harvested and reactive oxygen species (ROS) obtained, the ALHSs employ a multi-step sequential energy transfer process to enhance Minisci-type alkylation reactions with aldehydes through photocatalysis for late-stage functionalization in an aqueous environment, achieving a 91% yield.

Facile bio-inspired fabrication of AgNPs from Salvia elegans leaf extract and determination of their cytotoxic DNA photocleavage potential

This study introduces a sustainable method for producing silver nanoparticles (AgNPs), focusing on sustainability and environmental protection. The technique includes the use of Salvia elegans aqueous leaf extract as a reducing agent. In addition, the research investigates the dose-dependent degradation of pUC19 DNA by silver nanoparticles, which is facilitated by the generation of singlet oxygen. The presence of S. elegans extract results in significant color changes, going from a colorless state to a dark brown hue, serving as an indication of the synthesis of AgNPs. A range of experimental methods were employed to analyze the biogenic silver nanoparticles, such as UV–visible absorption spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The meticulously produced AgNPs demonstrate a high level of uniformity, featuring a spherical shape and a particle size of 60 nm. DNA photo-cleavage studies show that singlet oxygen plays a crucial role in triggering DNA damage caused by AgNPs indicates their potential as powerful cytotoxic agents specifically aimed at cancer cells. Additional studies are required to clarify the effectiveness and specificity of AgNPs against various cancer cell types to assess their therapeutic potential. The cytotoxic effects of AgNPs, particularly in relation to DNA photocleavage, are of considerable interest in cancer research. This research holds promise for developing novel and sustainable cancer therapies based on the unique properties of biogenic silver nanoparticles.

A new Rose Bengal glycopolymer: Photosensitization in two stages

Antimicrobial photodynamic therapy is a promising alternative to deal with antimicrobial resistance. However, both the low specificity and low local oxygen molecular concentrations decrease the antimicrobial efficiency limiting its use. An interesting approach to the problem is the use of molecules that can react reversibly with singlet oxygen by the formation of reversible endoperoxides, such as naphthalene, anthracene and pyridone derivatives. Particularly, the use of these molecules with mannosyl derivatives allow the interaction with adhesins presented on pili and fimbriae improving the localization near to bacteria. In this work, we synthesized polymeric nanoparticles able to generate singlet oxygen (under both irradiation and dark conditions) in the vicinity of a center capable of recognizing mannose and oxidize nearby biomolecules. Rose Bengal was used as photosensitizer due to its attractive photophysical properties (vis absorption, high singlet oxygen generation) and biocompatibility. The polymeric nanoparticles were obtained by radical polymerization using polyvinyl alcohol as a template, showing sizes around 300 nm with negative zeta potential by dynamic light scattering. The singlet oxygen generation was monitored following DPBF consumption and showed to be dependent on the amount of pyridone in the feed of polymers. In addition, the release of singlet oxygen was also dependent on pyridone concentration showing a slower rate constant at 40 % pyridone, while for contents of 10 % and 60 % higher rate constants were observed. The specific interaction of glycopolymers with Concanavalin A was demonstrated by successful agglutination assays, but also a low participation of unspecific interactions for polymers without mannosyl derivatives was observed. On the other hand, the oxidation of amino acids of Concanavalin A was monitored by acrylamide gel electrophoresis. Type I and Type II photosensitization were observed with the formation of dimers and fragments with lower molecular weight, while in dark conditions only products with lower molecular weight were observed, result consistent with singlet oxygen released by pyridone endoperoxides.

Surface electric fields-enhanced biochar: A dual-action adsorbent and PMS activator for sulfamethoxazole removal

Integrating adsorption with advanced oxidation processes offers significant advantages over conventional single-stage wastewater treatment methodologies. Herein, this study successfully synthesized nitrogen-boron codoped metal-free biochar at 700 °C (700NBBC). 700NBBC effectively eliminates sulfamethoxazole (SMX) from water through a synergistic adsorption-oxidation process, showcasing robust resistance to interference and broad pH tolerance. Characterizations and experimental outcomes indicate that 700NBBC primarily adsorbs SMX through a monolayer surface chemical adsorption mechanism and activates persulfate (PMS) to oxidize SMX via a non-radical mechanism, which includes the generation of singlet oxygen (1O2) and electron transfer processes. Density functional theory calculations elucidate that N and B doping regulate the local electronic environment at biochar surface, enhancing the adsorption energy between biochar and PMS while effectively catalyzing PMS cleavage to generate 1O2. This research offers fresh perspectives on the critical role of heteroatom doping in regulating reactive oxygen species generation within biochar.

Photophysical characterization of xanthene dyes

The growing interest in using photodynamic therapy for cancer treatment and antimicrobial applications has prompted the search for different classes of dyes. In general, the protocols of these studies are different, making it difficult to compare their efficiency directly. Here, we apply a controlled protocol to analyze the photophysical properties of Erythrosin B, Eosin Y, and Rose Bengal using a set of optical techniques. The results show that Erythrosine has the best singlet oxygen generation capacity. This result, added to the well-known low toxicity of Erythrosine, makes it a good choice among the xanthenes for health applications.

Carbon defect induced electron transfer promotes electrocatalytic activation of molecular oxygen to selectively generate singlet oxygen for pollutants removal

This study explored the design of heterojunctions incorporating defective graphene and boron nitride (BN) to activate molecular oxygen (O₂) and degrade sulfamethoxazole (SMX) by establishing efficient electron transport channels. These heterojunction catalysts, designed using theoretical predictions, were synthesized by controlling carbon defect concentration and pyrolysis temperature. The optimized GBN cathode achieved a maximum SMX degradation rate of 0.0252min⁻¹, with a total organic carbon (TOC) removal efficiency of 47.31%. Singlet oxygen (¹O₂) was identified as the primary reactive oxygen species, exhibiting a generation rate of 18.66μMmin⁻¹ and contributing 93.5% to SMX degradation. Results demonstrated that an optimal defect concentration enhances electron transfer, promoting the 2-electron reduction of O₂ to H₂O₂ and facilitating further H₂O₂ activation, thereby accelerating SMX degradation. This work advances the development of non-metallic cathodic catalysts and provides valuable insights into electrochemical degradation mechanisms for organic pollutants.

Zinc phthalocyanine-bridged periodic mesoporous organosilica nanoparticle as biodegradable photosensitizer for photodynamic therapy

The development of efficient photosensitizers is vital for advancing photodynamic therapy (PDT), a non-invasive cancer treatment. Although zinc phthalocyanine (ZnPc) has garnered significant attention as a photosensitizer in preclinical studies, its clinical application is hindered by poor solubility and a tendency to aggregate, despite its high absorption coefficient and low dark toxicity. To address these challenges, we developed a novel ZnPc-conjugated periodic mesoporous organosilica (PMO) nanoparticle, which enhances the photosensitizer's solubility, photostability, and biodegradability. The PMO nanoparticles retained the characteristic mesoporous structure, exhibited strong fluorescence emission, and effectively generated singlet oxygen. In vitro studies using 4T1 cells, along with in vivo experiments on a tumor-bearing mouse model, demonstrated that under 675nm laser irradiation, the ZnPc-PMO nanophotosensitizer induced reactive oxygen species, leading to significant inhibition of tumor growth. This ZnPc-bridged PMO nanophotosensitizer holds great promise for enhancing PDT efficacy and biocompatibility, offering a potential platform for multimodal phototherapeutic strategies.

Unveiling the potent Antimicrobial Photodynamic Therapy in Gram-positive and Gram-negative bacteria – Water remediation with monocharged chlorins

Water pollution is a significant concern worldwide, and it includes contaminants such as antibiotic-resistant pathogens. Antimicrobial photodynamic therapy (aPDT) offers a non-invasive and non-toxic alternative for the inactivation of these microorganisms. So, this study reports the synthesis, structural characterisation, photophysical properties, and aPDT efficacy of cationic free-base and zinc(II) chlorin (Chl) derivatives bearing N,N-dimethylpyrrolydinium groups (H2Chl 1a and ZnChl 1b). The aPDT assays were performed against two bacterial models: Staphylococcus aureus (Gram-(+)) and Escherichia coli (Gram-(–)). The H2Chl 1a and ZnChl 1b distinct’s solubility profile, coupled with their ability to generate singlet oxygen (1O2) under light exposure, (H2Chl 1a, ФΔ = 0.58 <TPP, ФΔ = 0.65 < ZnChl 1b, ФΔ = 0.83) opens up their potential application as photosensitizers (PS) in aPDT. The effectiveness of H2Chl 1a and ZnChl 1b at 1.0 and 5.0 μM in aPDT against S. aureus and E. coli at 500 W.m–2 (total exposure time: 60 –120 min) showed a viability reduction > 6.0 log10 CFU.mL–1. Additionally, KI was used as a coadjuvant to potentiate the photoinactivation of E. coli, reaching the method’s detection limit (> 4.0 log10 RLU). As most of the PS developed to inactivate Gram-negative bacteria are cationic with three or more charges, the fact that the H2Chl 1a and ZnChl 1b with only one cationic charge photoinactivate E. coli at low concentrations and with a reduced light dose, it is an importing discovery that deserves further exploration. These monocharged chlorin dyes have the potential for water remediation.

Dual-Mode Reactive Oxygen Species-Stimulated Carbon Monoxide Release for Synergistic Photodynamic and Gas Tumor Therapy.

Controllable carbon monoxide (CO) release simulated by light-generated reactive oxygen species (ROS) represents a promising approach for cancer therapy but is hampered by low CO release rate and low ROS generation of conventional photosensitizers in hypoxia tumor microenvironments. In this study, we developed a highly efficient nanoplatform (TPyNO2-FeCO NPs) through co-encapsulating organic AIE photosensitizers (PSs) and CO prodrug (Fe3(CO)12), which are capable of light-triggered robust ROS generation and CO release for synergistic photodynamic therapy (PDT) and CO gas therapy. The success of this nanoplatform leverages the design of a PS, TPyNO2, with exceptional type I and type II ROS generation capabilities, achieved through the introduction of the α-photoinduced electron transfer (α-PET) process. With the incorporation of a 4-nitrobenzyl unit as a typical PET donor, the intramolecular α-PET process not only suppresses the radiative decay to redirect the excited-state energy to intersystem crossing for more triplet-state formation but also promotes electron separation and transfer processes for radical-type ROS generation. The resultant TPyNO2 demonstrates superior singlet oxygen, superoxide anion, and hydroxyl radial generation capabilities in the aggregate state. Upon light irradiation, TPyNO2-FeCO NPs release CO via the type I and type II dual-mode ROS-mediated processes in a controlled and targeted manner, overcoming the limitations of conventional CO release systems. TPyNO2-FeCO NPs also demonstrate a self-accelerating ROS-CO-ROS loop as the released CO induces intracellular oxidative stress, depolarizes mitochondria membrane potentials, and inhibits ATP production, leading to further intracellular ROS generation. Both in vitro and in vivo experiments validated the excellent antitumor performance of the combined PDT and CO gas therapy. This study provides valuable insights into the development of advanced PSs and establishes TPyNO2-FeCO NPs as promising nanoplatforms for safe and effective antitumor applications.