1O2 Production Research Articles

Carbon Nitride Supported High‐Loading Fe Single‐Atom Catalyst for Activation of Peroxymonosulfate to Generate 1O2 with 100 % Selectivity

AbstractSinglet oxygen (1O2) is an excellent active species for the selective degradation of organic pollutions. However, it is difficult to achieve high efficiency and selectivity for the generation of 1O2. In this work, we develop a graphitic carbon nitride supported Fe single‐atoms catalyst (Fe1/CN) containing highly uniform Fe‐N4 active sites with a high Fe loading of 11.2 wt %. The Fe1/CN achieves generation of 100 % 1O2 by activating peroxymonosulfate (PMS), which shows an ultrahigh p‐chlorophenol degradation efficiency. Density functional theory calculations results demonstrate that in contrast to Co and Ni single‐atom sites, the Fe‐N4 sites in Fe1/CN adsorb the terminal O of PMS, which can facilitate the oxidization of PMS to form SO5.−, and thereafter efficiently generate 1O2 with 100 % selectivity. In addition, the Fe1/CN exhibits strong resistance to inorganic ions, natural organic matter, and pH value during the degradation of organic pollutants in the presence of PMS. This work develops a novel catalyst for the 100 % selective production of 1O2 for highly selective and efficient degradation of pollutants.

Molecular Structural Evolution of Near-Infrared Cationic Aggregation-Induced Emission Luminogens: Preclinical Antimicrobial Pathogens Activities and Tissues Regeneration

Molecular Structural Evolution of Near-Infrared Cationic Aggregation-Induced Emission Luminogens: Preclinical Antimicrobial Pathogens Activities and Tissues Regeneration

Dual Reactive Oxygen Species Generator Independent of Light and Oxygen for Tumor Imaging and Catalytic Therapy

Dual Reactive Oxygen Species Generator Independent of Light and Oxygen for Tumor Imaging and Catalytic Therapy

Arsenene-mediated multiple independently targeted reactive oxygen species burst for cancer therapy

The modulation of intracellular reactive oxygen species (ROS) levels is crucial for cellular homeostasis and determination of cellular fate. A sublethal level of ROS sustains cell proliferation, differentiation and promotes tumor metastasis, while a drastic ROS burst directly induces apoptosis. Herein, surface-oxidized arsenene nanosheets (As/AsxOy NSs) with type II heterojunction are fabricated with efficient ·O2− and 1O2 production and glutathione consumption through prolonging the lifetime of photo-excited electron-hole pairs. Moreover, the portion of AsxOy with oxygen vacancies not only catalyzes a Fenton-like reaction, generating ·OH and O2 from H2O2, but also inactivates main anti-oxidants to cut off the “retreat routes” of ROS. After polydopamine (PDA) and cancer cell membrane (M) coating, the engineered As/AsxOy@PDA@M NSs serve as an intelligent theranostic platform with active tumor targeting and long-term blood circulation. Given its narrow-band-gap-enabled in vivo fluorescence imaging properties, As/AsxOy@PDA@M NSs could be applied as an imaging-guided non-invasive and real-time nanomedicine for cancer therapy.

Singlet oxygen formation during accelerated and hyperaccelerated corneal cross-linking: in vitro study.

To evaluate the singlet oxygen (1O2) production of oxygen assisted %0.1 riboflavin and ultraviolet-A (UVA) crosslinking therapy (with and without oxygen assistance), in combination with standard, accelerated and hyper-accelerated procedures via an important quantitive marker of 1O2 which is the photo-oxidation of 1,3 diphenylisobenzofuran (DPBF). %0.1 riboflavin-containing wells were irradiated with UVA light (365-nm wavelength) with or without 2-4-6-8 L/min oxygen flow assistance. Measurements of decrease in absorbance of DPBF were made in 30 mW (hyper-accelerated), 9 mW (accelerated), and 3 mW UV-A (standard) applications, and with additional 2-4-6-8 L/min oxygen flow in 30 mW and 2 L/min oxygen flow in 9 mW. A total of 8 different UV-A irradiance with and without oxygen supplementation groups were formed. 2 L/min oxygen assisted accelerated UV-A irradiance group has shown a greater decrease in DPBF absorbance compared to Dresden protocol. (p = 0.014) Also, Dresden protocol has shown a greater decrease in DPBF compared to all groups except accelerated crosslinking with 2 L/min oxygen. (p < 0.001) Oxygen assisted hyper-accelerated crosslinking groups were showed greater reduction in DPBF absorbance compared to standard crosslinking without oxygen groups. (p < 0.001). Oxygen supplementation may increase the singlet oxygen generation to the similar levels of Dresden Protocol's in accelerated group. Also, more singlet oxygen generation with oxygen supplementation compared to standard UV-A application might be considered to be promising in terms of shortening the crosslinking therapy.

Identifying high performance gold nanoshells for singlet oxygen generation enhancement

Metallic nanostructures can improve the production of singlet oxygen (1O2) of a photosensitizer during photodynamic therapy (PDT) . Engineering a high performance nanoparticle is mandatory for an appropriate use of plasmonic nanostructures in PDT. Metal enhanced singlet oxygen generation requires the use of nanoparticles with high scattering efficiency, capable of inducing a significant electric field enhancement and with plasmon peak overlapping the photosensitizer absorption spectrum. Herein, we report the optimization of nanoshells structure (silica core radius and gold shell thickness) to increase the singlet oxygen production by Methylene Blue photosensitizer. A 3D Full-wave field analysis was used to evaluate the plasmonic spectrum, scattering efficiency and localized field intensity of Au nanoshells as a function of their dimensions. The 40/20 core radius/shell thickness optimized gold nanoshell showed 75% scattering efficiency and field enhancement up to 35 times. Metal-enhanced singlet oxygen generation was observed and quantified for Methylene Blue water solution with gold nanoshell particles. Moreover, the influence of the irradiation time and the metallic nanostructures concentration on metal enhanced singlet oxygen generation were also appraised. The experimental results showed that the use of gold nanoshell improved 320% the 1O2 production in a MB solution. The approach used to select a high performance metallic nanoparticle provides insights on engineering plasmonic structures for metal enhanced singlet oxygen generation for PDT.

A Compartmental Silica Nanoreactor for Multienzyme‐Regulated Superactive Catalytic Therapy

AbstractMany tumor therapies take advantage of upsetting the redox balance in tumor cells, but to do so requires excessive biochemical or physical attacks. The high‐throughput simulation using multi‐pathway techniques described herein can yield an increased efficacy in bio‐oxidation. In this study, compartmental hierarchical nanoreactors are developed as an efficient multi‐pathway singlet oxygen (1O2) generation system for superactive biocatalytic tumor therapy. The penetrated super cavity and connected dual‐mesopore channels of the compartmental multienzyme nanoreactors are designed using the proposed heterogeneous template assembly for multi‐enzyme complex (superoxide dismutase (SOD)‐lactoperoxidase (LPO)) and photosensitizer molecule (indocyanine green (ICG)) encapsulation. Benefiting by the enhanced direct substrate diffusion between the interacting SOD–LPO complex and decrease in external diffusion, the parallel catalysis combined by the superactive cascade biocatalysis and enzyme‐promoted photosensitization effect is verified by this compartmental silica nanoreactor system. The parallel pathways not only make full use of the products of SOD (H2O2 and O2), but also exhibit outstanding capability for 1O2 production, at ≈2.15 and 1.70 times augmented 1O2, respectively. Both in vitro and in vivo studies demonstrate the synergetic 1O2‐mediated inhibition of tumor proliferation, lending this strategy great potential for the treatment of hypoxic tumors.

Peroxymonosulfate/LaCoO3 system for tetracycline degradation: Performance and effects of co-existing inorganic anions and natural organic matter

The activation of peroxymonosulfate (PMS) has been developed as an efficient method for the degradation of antibiotics by generating reactive oxygen species (ROS), where perovskite oxides have been found as effective catalysts. However, the reaction mechanism, degradation pathways, as well as the effects of co-existing inorganic anions and natural organic matter are largely unknown. Therefore, the degradation efficiency and mechanism of tetracycline (TC) through the activation of PMS by LaCoO3 were investigated. Moreover, the effects of common inorganic anions and natural organic matter (e.g., humic acid (HA)) on degradation efficiency were also compared. Without the presence of coexisting substance, TC removal exceeded 90% within 30 min, while 72% mineralization was achieved in 6 h, under optimal reaction conditions at neutral pH. In addition to the traditional free radicals of OH and SO4−, 1O2 and O2− also contributed the degradation process, where the lattice oxygen of LaCoO3 played a significant role in 1O2 production. The degradation of TC followed the pathways including demethylation, hydroxylation and ring-opening reactions. The presence of inorganic anions (i.e., H2PO4−, Cl− and SO42−) and low-concentration of HA promoted the degradation. Among them, H2PO4− and lower concentration of HA showed the most obvious outcome, while the SO42− can regulate the radical formation, minimize the peak radical level, and therefore promote the overall performance of the process. LaCoO3 exhibited stable reusability with minor decrease in TC removal, likely due to the adsorption of intermediate products from previous stages. These obtained results shed light on the application of perovskite oxides for PMS activation on removing antibiotics.

Quenching effects of (-)-Epigallocatechin gallate for singlet oxygen production and its protection against oxidative damage induced by Ce6-mediated photodynamic therapy in vitro

BackgroundSinglet oxygen (1O2) is highly reactive to biological components such as lipids, proteins and DNA, which induces oxidative damage to cells and tissues. Natural antioxidants may function as 1O2 quencher to prevent 1O2 involved photosensitized oxidation in biological system. MethodsTime-resolved measurement of 1O2 luminescence was employed to evaluate the 1O2 quenching abilities of natural antioxidants in air-statured phosphate buffered saline (PBS), including (-)-Epigallocatechin gallate (EGCG), Proanthocyanidins, L-carnosine and Vitamin C. The 1O2 quenching effects and rate constant of EGCG were investigated by detecting the absorption, fluorescence and 1H-NMR spectroscopy and 1O2 luminescence decay curves, respectively. In addition, the protective activity of EGCG against 1O2 oxidative damage caused by Ce6-mediated photodynamic therapy (PDT) was verified in cells. ResultsEGCG, proanthocyanidins, L-carnosine and Vitamin C efficiently quenched 1O2 luminescence at 1270 nm. The triplet-state quenching rate constants of EGCG for Rose Bengal (RB), Chlorin e6, AlPcS and HiPorfin are 2.21 × 109, 4.90 × 108, 3.30 × 108, 1.78 × 109 M−1s−1, while the 1O2 quenching rate constants are 2.80 × 108, 1.50 × 108, 1.30 × 108, 1.70 × 108 M−1s−1, respectively. Furthermore, EGCG could effectively quench 1O2 production to prevent NIH/3T3 cells oxidative damage induced by Ce6-mediated PDT. ConclusionsEGCG is an efficient quencher for both triplet-state photosensitizers and 1O2. The quenching ability of EGCG during photosensitization for selected photosensitizers is: RB > HiPorfin > Ce6 > AlPcS. EGCG could be used to protect normal cells and tissue against oxidative damage.

Recent Research Trends of Two‐Photon Photosensitizer for Simultaneous Imaging and Photodynamic Therapy

Imaging and photodynamic therapy through two‐photon excitation can be applied to medical application of deep inside the tissue by minimizing light absorption by the tissue. It is the best solution that can complement the shortcomings of conventional photodynamic therapy. In addition, auto‐fluorescence can be minimized, and damage to normal cells can be avoided through spatial and temporal control. To maximize the image realization and the effect of treatment, a single photosensitizer with high fluorescence quantum yields, two‐photon absorption value, and good 1O2 or reactive oxygen species production performance must be developed. Therefore, recent research related to this topic is summarized. In addition, two‐photon photosensitizers that approach selective imaging and treatment for target diseases and future challenges were discussed.

Catalytically Active CoFe2O4 Nanoflowers for Augmented Sonodynamic and Chemodynamic Combination Therapy with Elicitation of Robust Immune Response.

A hypoxic and acidic tumor microenvironment (TME) plays a significant role in cancer development through complex cellular signaling networks, and it is thus challenging to completely eradicate tumors via monotherapy. Here, PEGylated CoFe2O4 nanoflowers (CFP) with multiple enzymatic activities, serving as bioreactors responsive to TME cues, were synthesized via a typical solvothermal method for augmented sonodynamic therapy (SDT) and chemodynamic therapy (CDT) with elicitation of robust immune response. The CFP occupying multivalent elements (Co2+/3+, Fe2+/3+) exhibited strong Fenton-like and catalase-like activity. In another aspect, CFP itself is a brand-new sonosensitizer for high-performance SDT based on ultrasound-triggered electron (e-)/hole (h+) pair separation from the energy band with promptness and high efficiency. With efficient enrichment in tumorous tissue as revealed by magnetic resonance imaging, CPF could generate •OH for CDT relying on Fenton-like reactions. Moreover, catalase-mimicking CFP could react with endogenous H2O2 to generate molecular oxygen, and high O2 level may promote the production of 1O2 for SDT. What's more, the reactive oxygen species obtained from combined SDT/CDT could efficiently trigger immunogenic cell death through a synergistic therapy based on the elicitation of antitumor immunity with the aid of an immune checkpoint blockade for the sake of suppressing primary and distant tumors as well as lung metastasis. Taken together, this paradigm delivers useful insights for developing in-coming nanocomposites based on cobalt ferrite for cancer theranostics.

Photosensitive Ru(II) Complexes as Inhibitors of the Major Human Drug Metabolizing Enzyme CYP3A4.

We report the synthesis and photochemical and biological characterization of the first selective and potent metal-based inhibitors of cytochrome P450 3A4 (CYP3A4), the major human drug metabolizing enzyme. Five Ru(II)-based derivatives were prepared from two analogs of the CYP3A4 inhibitor ritonavir, 4 and 6: [Ru(tpy)(L)(6)]Cl2 (tpy = 2,2':6',2″-terpyridine) with L = 6,6'-dimethyl-2,2'-bipyridine (Me2bpy; 8), dimethylbenzo[i]dipyrido[3,2-a:2',3'-c]phenazine (Me2dppn; 10) and 3,6-dimethyl-10,15-diphenylbenzo[i]dipyrido[3,2-a:2',3'-c]phenazine (Me2Ph2dppn; 11), [Ru(tpy)(Me2bpy)(4)]Cl2 (7) and [Ru(tpy)(Me2dppn)(4)]Cl2 (9). Photochemical release of 4 or 6 from 7-11 was demonstrated, and the spectrophotometric evaluation of 7 showed that it behaves similarly to free 4 (type II heme ligation) after irradiation with visible light but not in the dark. Unexpectedly, the intact Ru(II) complexes 7 and 8 were found to inhibit CYP3A4 potently and specifically through direct binding to the active site without heme ligation. Caged inhibitors 9-11 showed dual action properties by combining photoactivated dissociation of 4 or 6 with efficient 1O2 production. In prostate adenocarcinoma DU-145 cells, compound 9 had the best synergistic effect with vinblastine, the anticancer drug primarily metabolized by CYP3A4 in vivo. Thus, our study establishes a new paradigm in CYP inhibition using metalated complexes and suggests possible utilization of photoactive CYP3A4 inhibitory compounds in clinical applications, such as enhancement of therapeutic efficacy of anticancer drugs.

Red emissive two-photon carbon dots: Photodynamic therapy in combination with real-time dynamic monitoring for the nucleolus

Treatment in combination with real-time monitoring of dynamic organelle changes is of great significance for evaluating therapeutic efficacy. However, it remains highly challenging to realize such specific treatment and monitoring in organelles. Herein, we developed one kind of red emissive two-photon carbon dots (TP-CDs) via an N doping strategy for nucleolus-targeted treatment combined with real-time monitoring of dynamic changes in the nucleolus. In the TP-CD system, N doping endows TP-CDs with intrinsic two-photon excitation, red emission at 605 nm, and singlet oxygen (1O2) production under 638 nm laser irradiation. More importantly, N heterocycles induced by doping offers significant affinity for TP-CDs toward RNA to realize specific self-targeting toward nucleolus and fluorescence variation during the photodynamic therapy (PDT) via the cleaving of RNA chain by 1O2 to dissociate TP-CDs@RNA complex. By combining 1O2 production, fluorescent variation during the PDT process, long-wavelength excitation and emission characteristics, as well as specific self-targetability of nucleolus, TP-CDs can be considered as a kind of “smart” CDs to realize treatment in combination of real-time dynamic changes in nucleolus for the first time.

Nanobody modified high-performance AIE photosensitizer nanoparticles for precise photodynamic oral cancer therapy of patient-derived tumor xenograft

Photodynamic therapy (PDT) is a promising noninvasive treatment option for patients suffering from superficial tumors, such as oral cancer. However, for photosensitizers (PSs), it remains a grand challenge to simultaneously excel in all the key performance indicators including effective singlet oxygen (1O2) generation under clinical laser, specific targeting function and stable far-red (FR)/near-infrared (NIR) emission with low dark toxicity. In addition, traditional PS nanoparticles (NPs) for clinical use suffer from quenched fluorescence and reduced 1O2 production caused by molecular aggregation. To address these issues, AIEPS5 with aggregation-induced FR/NIR emission and effective 1O2 generation under 532 nm laser irradiation is designed by precise optimization of the chemical structure. By attaching a polyethylene glycol (PEG) chain onto AIEPS5, the yielded amphiphilic AIEPS5-PEG2000 can spontaneously self-assemble into water dispersible NPs, which are further endowed with targeted delivery function via the decoration of anti-Her-2 nanobody (NB). The bespoke AIEPS5-NPs-NB exhibit effective 1O2 generation capability, bright FR/NIR emission centered at 680 nm, and negligible dark toxicity, which outperform Heimbofen, a clinically approved PS in PDT using a patient-derived tumor xenograft model.

Plasma membrane targeted photodynamic O2 economizer for hypoxic tumor therapy

The development of photodynamic therapy (PDT) is severely limited by short half-life of singlet oxygen (1O2) and the hypoxic microenvironment. In this work, a plasma membrane targeted photodynamic O2 economizer (designated as P-POE) is developed to improve the subcellular delivery of photosensitizers and alleviate the tumor hypoxia for enhanced PDT effect. After self-assembly into nanomicelles, P-POE has a relatively high stability and a favorable photochemical performance, which are conducive to boosting the 1O2 production. Besides, the plasma membrane anchoring of P-POE contributes to enhancing the preferential retention and cellular accumulation of photosensitizers on tumor tissues and cells. More importantly, P-POE-induced mitochondrial respiratory depression is demonstrated to reduce the O2 consumption of tumor cells to relieve the hypoxia. Consequently, P-POE still exhibits a robust PDT effect against hypoxic tumors, which greatly inhibits the proliferation of breast cancer with low adverse reactions. This innovative combination of subcellular targeting and hypoxic alleviation would advance the development of individualized drug delivery systems for photodynamic therapy against hypoxic tumors.

Multitherapeutic nanoplatform based on scintillating anthracene, silver@anthracene, and gold@anthracene nanoparticles for combined radiation and photodynamic cancer therapies

We have synthesized anthracene and metal@anthracene core-shell nanoparticles to combine radiation (RT) and photodynamic (PDT) therapies. Synthesis of anthracene nanoparticles in the presence of colloidal silver or gold reduced the nanoparticles hydrodynamic radius, caused core-shell nanostructures to grow, and led to plasmon-enhanced fluorescence. Singlet oxygen (1O2) generation was investigated by electron spin resonance (ESR) and fluorescence spectroscopies. In the presence of a porphyrin, anthracene nanoparticles and the core-shell nanoparticles acted as energy mediators and increased 1O2 generation under exposure to light, as evidenced by the ESR results. Fluorescence suppression experiments showed that the core-shell nanoparticles captured 1O2 at rates higher than anthracene nanoparticles, suggesting that overall production of 1O2 (1O2 captured by spin-trap + 1O2 captured by surface anthracene molecules) was higher for the core-shell nanoparticles. Moreover, the Ag@anthracene nanoparticles stood out as a new and more sensitive fluorescent probe for 1O2. During irradiation with X-rays, both anthracene and Ag@anthracene nanoparticles trapped 1O2; subsequently, they afforded sustained release of the trapped 1O2 for up 12 days after irradiation. This could be an interesting strategy to extend the radiation therapy treatment after the irradiation sessions. Furthermore, the presence of the metallic nanoparticle in the core of the core-shell nanostructure increased interaction with X-rays, raising the radiation dose around the nanoparticle. Therefore, metal@anthracene nanostructures may allow combination of cancer treatments by different approaches depending on the adopted nanoparticle configuration.

Building Block Symmetry Relegation Induces Mesopore and Abundant Open-Metal Sites in Metal–Organic Frameworks for Cancer Therapy

Building Block Symmetry Relegation Induces Mesopore and Abundant Open-Metal Sites in Metal–Organic Frameworks for Cancer Therapy

Redox-responsive nanoparticles self-assembled from porphyrin-betulinic acid conjugates for chemo- and photodynamic therapy

The redox-responsive nanoparticle (NanoP-ss-BA) is designed by linking the porphyrin derivative (P) to the naturally occurring betulinic acid (BA) through a disulphide bond. A GSH triggered disassembly of NanoP-ss-BA effectively promotes a singlet oxygen (1O2) production, but also releases lipophilic anticancer drug, BAin situ. Beside this, high phototoxicity of NanoP-ss-BA serves it as a good candidate for photodynamic therapy (PDT).

Evolution of Singlet Oxygen by Activating Peroxydisulfate and Peroxymonosulfate: A Review.

Advanced oxidation processes (AOPs) based on peroxydisulfate (PDS) or peroxymonosulfate (PMS) activation have attracted much research attention in the last decade for the degradation of recalcitrant organic contaminants. Sulfate (SO4•−) and hydroxyl (•OH) radicals are most frequently generated from catalytic PDS/PMS decomposition by thermal, base, irradiation, transition metals and carbon materials. In addition, increasingly more recent studies have reported the involvement of singlet oxygen (1O2) during PDS/PMS-based AOPs. Typically, 1O2 can be produced either along with SO4•− and •OH or discovered as the dominant reactive oxygen species (ROSs) for pollutants degradation. This paper reviews recent advances in 1O2 generation during PDS/PMS activation. First, it introduces the basic chemistry of 1O2, its oxidation properties and detection methodologies. Furthermore, it elaborates different activation strategies/techniques, including homogeneous and heterogeneous systems, and discusses the possible reaction mechanisms to give an overview of the principle of 1O2 production by activating PDS/PMS. Moreover, although 1O2 has shown promising features such as high degradation selectivity and anti-interference capability, its production pathways and mechanisms remain controversial in the present literatures. Therefore, this study identifies the research gaps and proposes future perspectives in the aspects of novel catalysts and related mechanisms.

A Bio‐Conjugated Fullerene as a Subcellular‐Targeted and Multifaceted Phototheranostic Agent

AbstractFullerenes are candidates for theranostic applications because of their high photodynamic activity and intrinsic multimodal imaging contrast. However, fullerenes suffer from low solubility in aqueous media, poor biocompatibility, cell toxicity, and a tendency to aggregate. C70@lysozyme is introduced herein as a novel bioconjugate that is harmless to a cellular environment, yet is also photoactive and has excellent optical and optoacoustic contrast for tracking cellular uptake and intracellular localization. The formation, water‐solubility, photoactivity, and unperturbed structure of C70@lysozyme are confirmed using UV‐visible and 2D 1H, 15N NMR spectroscopy. The excellent imaging contrast of C70@lysozyme in optoacoustic and third harmonic generation microscopy is exploited to monitor its uptake in HeLa cells and lysosomal trafficking. Last, the photoactivity of C70@lysozyme and its ability to initiate cell death by means of singlet oxygen (1O2) production upon exposure to low levels of white light irradiation is demonstrated. This study introduces C70@lysozyme and other fullerene‐protein conjugates as potential candidates for theranostic applications.