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POULTRY SCIENCE · 2024 · IF 3.8

Sodium selenite antagonizes trimethyl tin-induced chicken hepatotoxic hepatitis through the RNS/NF-κB/NLRP3 pathway

Xinzhang Chen,Xu Lin

Trimethyl tin (TMT) is a good stabilizer for plastic products but is also a toxic environmental pollutant. Selenium has good antioxidant and anti-inflammatory properties and has been widely used in the poultry industry. However, it has not been reported whether selenium enrichment can antagonize TMT-induced viral hepatitis in poultry. To fill this gap, AA broiler models exposed to TMT for 42 d were established and fed a Se-enriched diet at the same time. H&E staining showed that selenium could significantly alleviate TMT-induced liver inflammation. Further analysis of the underlying mechanism revealed that TMT induced nitrosation stress (RNS), increased NO content and iNOS expression, which in turn activated the NF-κB/NLRP3 pathway and induced pyroptosis. However, selenium enrichment can reverse this situation, that is, reduce the occurrence of RNS, reduce the degree of pyroptosis, and thus alleviate the occurrence of inflammation. In our study, we demonstrated for the first time that TMT could induce hepatotoxicity other than neurotoxicity in poultry and that selenium could antagonize TMT-induced hepatotoxic hepatitis in chickens through the RNS/NF-κB/NLRP3 pathway.

CAS / MDL: 1066-45-1
研究领域: 毒理学 · 兽医学 · 分子生物学
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2024 · IF 5.7

New Insights into the Toxic Effects of Different Sizes of Nanosilica Particles in Food on the Mouse Bladder: Involving Epithelial–Mesenchymal Transition

Yilin Yin,Jiaqi Wang,Tong Xu,Meichen Liu,Xu Shi,Shiwen Xu

Animals are widely exposed to nanosilica as a food additive. However, the negative effects of such nanosilica particles on animals’ bladders are unclear. In the present study, we investigated the impact of MPs-SiO2 on mouse bladder and the underlying mechanisms. Mouse and MBEC cell models exposed to MPs-SiO2 with different particle sizes were established. At the same time, aminoguanidine hydrochloride (RNS inhibitor) and NF-κB activator were used to further explore its mechanism in vitro. We found that MPs-SiO2 of three sizes could induce RNS-induced pyroptosis causing EMT both in vitro and in vivo. After inhibiting RNS, the expression of related proteins in downstream pathways was decreased, and fibrosis was alleviated. The above situation was reversed by the addition of NF-κB activator. Furthermore, our data suggest that 300 nm MPs-SiO2 particles have a greater impact on the bladder than 50 nm particles. This study revealed the potential health risks of MPs-SiO2 and provided new insights into the toxicology of MPs-SiO2.

CAS / MDL: 1937-19-5
研究领域: 毒理学 · 分子生物学 · 医学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Journal of Materials Chemistry B · 2017 ·Vol. 5 ·期 46 ·9197-9203 · IF 4.543

Silica nanoparticles based on an AIE-active molecule for ratiometric detection of RNS in vitro

Leijing Liu,Fengli Zhang,Bin Xu,Wenjing Tian

Nitric oxide (NO), known as a reactive nitrogen species (RNS), has been considered to be a significant factor in many cell-related biological processes. There is a great desire to develop fluorescent probes that can highly sensitively and selectively detect NO in living cells. Herein, a fluorescent probe, a tetraphenylethene (TPE) derivative TPE-2NH2, with aggregation induced emission (AIE) properties was designed and synthesized. Then silica nanoparticles based on TPE-2NH2 were fabricated for ratiometric detection of NO in vitro with high sensitivity and selectivity. In the presence of NO, the fluorescence of the silica nanoparticles changes from 519 nm (green) to 655 nm (red) because of the chemical reaction between NO and o-phenylenediamine in TPE-2NH2. The silica nanoparticles exhibited very high sensitivity and selectivity towards NO in aqueous buffer, and the response time was as short as 5 minutes. Moreover, the silica nanoparticles can also highly sensitively and selectively respond to NO produced in living cells. When MCF-7 cancer cells were activated by lipopolysaccharides (LPS), which can effectively induce the production of NO, the red emission signal of the silica nanoparticles obviously increased. This demonstrated that the silica nanoparticles showed fine imaging contrast towards NO in MCF-7 cancer cells, which provides a facile tool to detect intracellular NO.

研究领域: 生物化学 · 分析化学 · 细胞生物学
✓ 已验证 DOI PubMed 高影响因子
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Biomaterials Science · 2021 ·Vol. 9 ·期 17 ·5824-5840 · IF 6.843

A NO/ROS/RNS cascaded-releasing nano-platform for gas/PDT/PTT/immunotherapy of tumors

Mengchao Ding,Kai Shao,Lijuan Wu,Yuping Jiang,Bing Cheng,Lili Wang,Jinsheng Shi,Xiaoying Kong

Nitric oxide (NO) gas treatment offers a promising strategy for tumor therapy; however, its practical application is still limited due to its poor efficacy and biotoxicity which were caused by gas leakage during blood delivery. Herein, a nano-platform (CMH-OBN) composed of chlorin e6-melanin-hyaluronic acid nanoparticles (Ce6-MNP-HA, CMH) and oxidized bletilla striata polysaccharide microcapsules (Oxi-BSP) carrying NO donors was prepared for responsive and cascaded release of NO, reactive oxygen species (ROS) and its secondary metabolite reactive nitrogen species (RNS) in tumor sites. Melanin not only endowed CMH with good photothermal properties, but also helped Ce6 to produce a large number of ROS under near-infrared (NIR) irradiation. OBN microcapsules, which were sensitive to ROS, can release NO donors under the stimulation of ROS released by CMH nanoparticles under NIR irradiation and can further release NO in the tumor microenvironment (TME) with high expression of glutathione (GSH). NO could further up-regulate soluble guanylate cyclase-cyclic guanosine monophosphate (sGC-cGMP) signal pathways to relieve hypoxia, thus further enhancing the photodynamic therapy (PDT). Moreover, the cascaded release of ROS and NO could produce RNS with higher lethality, which could sequentially initiate the cellular apoptotic procedure and promote immunotherapy by activating T cells at the tumor sites. More interestingly, the CMH-OBN nano-platform could supply magnetic resonance imaging (MRI) and infrared photothermal imaging guidance for tumor therapy. In conclusion, the development of a CMH-OBN nano-platform provides a satisfactory demonstration by combining NO therapy with photothermal therapy (PTT), PDT and immunotherapy for the treatment of cancer.

研究领域: 癌症治疗 · 纳米技术 · 生物医学工程 · 药学
✓ 已验证 DOI PubMed 高影响因子
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Small · 2025 · IF 12.1

Broad-Spectrum ROS/RNS Scavenging Catalase-Loaded Microreactors for Effective Oral Treatment of Inflammatory Bowel Diseases

Xiangyu Zhang,Yujie Zhu,Zijian Xiong,Wenjie Xie,Ming Shao,Zhuang Liu

Inflammatory bowel disease (IBD) such as ulcerative colitis (UC) is an autoimmune disease characterized by persistent inflammation along the gastrointestinal tract with excessive generation of reactive oxygen species (ROS)/reactive nitrogen species (RNS) generation. Here, catalase (CAT)-containing microreactor capsules with long-lasting broad-spectrum ROS/RNS-scavenging capability are developed for the treatment of IBD. In this design, CAT is encapsulated in the dense hydrogel network of calcium alginate (ALG) microspheres, which provides long-term protection of CAT activity in protease-rich intestinal environment. Afterward, the polydopamine (PDA) modification on the surface of CAT@ALG microspheres can provide them bioadhesiveness to achieve prolonged retention in the intestinal tract and broad-spectrum scavenging capability against various types of ROS/RNS beyond hydrogen peroxide. Enteric capsules are further used to protect the CAT@ALG–PDA microspheres from gastric fluid for selective release at the intestinal site. The combined action of PDA and CAT in CAT@ALG–PDA microreactors results in the broad-spectrum scavenging of excess ROS/RNS and regulates redox balance in acute UC rat model, showing satisfactory therapeutic effects superior to the mesalazine and adalimumab at clinically relevant doses without obvious side effects. This work highlights that these CAT@ALG–PDA capsules can act as long-acting broad-spectrum ROS/RNS reactors, promising for IBD treatment.

CAS / MDL: 62-31-7
研究领域: 医学 · 生物材料学 · 药剂学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

Biocompatible carbon dots nanozymes as ROS/RNS modulators for ulcerative colitis alleviation by comprehensively orchestrating intestinal homeostasis

Wenjing Wang,Guangrong Lu,Zhichao Deng,Huanyu Li,Wenfang He,Shouxing Yang,Yuanyuan Zhu,Chenxi Xu,Yujie Zhang,Lanqi Wang,Xiaoling Huang,Mingzhen Zhang,Changlong Xu

Ulcerative colitis (UC), a prevalent form of inflammatory bowel disease (IBD), is characterized by the presence of chronic, nonspecific, and recurring inflammation in the intestine. Current therapies are insufficient in addressing the effective modulation of the intestinal oxidative stress-inflammation cycle, the repair of the intestinal mechanical barrier, and the regulation of gut microbiota and metabolites. There is a need for a comprehensive approach to orchestrate intestinal homeostasis more effectively. For this purpose, biocompatible antioxidant carbon dots nanozymes (GH-CDs) were synthesized based on glucose and D-histidine using a microwave-assisted method for the systematic management of intestinal inflammation. It was demonstrated that GH-CDs possessed excellent reactive oxygen/nitrogen species (ROS/RNS) scavenging capacities, thus modulating oxidative stress-induced damage and mitigating inflammation by inhibiting the TNF, MAPK, PI3K-Akt, NF-κB, and JAK-STAT signaling pathways. For in vivo experiments, GH-CDs have demonstrated both protective and therapeutic effects in mitigating colitis by reducing ROS levels, decreasing the infiltration of M1-type macrophages, suppressing the release of pro-inflammatory cytokines, and repairing intestinal mechanical and chemical barriers. Importantly, GH-CDs also influenced the gut microbiome to achieve a more beneficial state, which was accomplished by enhancing bacterial diversity and altering the microbial composition towards an anti-inflammatory type. Additionally, GH-CDs supported the biosynthesis of secondary bile acids and isoflavonoids. In conclusion, with excellent biocompatibility, GH-CDs will be a promising strategy for UC by comprehensively orchestrating intestinal homeostasis.

研究领域: 生物医学工程 · 消化病学 · 纳米医学
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JOURNAL OF NANOBIOTECHNOLOGY · 2026 · IF 15

Cascade-activatable nano-prodrug amplifies ROS-RNS signaling to target NQO1-associated redox vulnerability for melanoma therapy

Tang Honglin,Wu Chongzhi,Wang Wei,Cheng Xi,Dong Yong,Gao Zhiyuan,Chen Pengfei,Xie Xin,Huang Yong,Sun Lihe,Li Bowen,Li Da

Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation (LPO), has emerged as a promising strategy for cancer therapy but remains limited by insufficient hydrogen peroxide (H₂O₂), restricted catalytic iron availability, and the extremely short lifetime of hydroxyl radicals (·OH) in the tumor microenvironment. Here, we report a self-assembled nano-prodrug designed to amplify oxidative stress through coordinated reactive oxygen species (ROS)-reactive nitrogen species (RNS) cascades. Transcriptomic analyses of melanoma cohorts revealed that the redox enzyme NAD(P)H: quinone oxidoreductase-1 (NQO1) is frequently upregulated and associated with oxidative stress and ferroptosis-related transcriptional programs, suggesting a potential redox vulnerability that can be therapeutically exploited. Guided by this observation, a glutathione-responsive nanoplatform (HFSAL) was constructed from a disulfide-bridged ferrocene–arginine scaffold (Fc-SS-Arg) with β-lapachone (β-lapa) co-loaded and hyaluronic acid coating for tumor-targeted delivery. Upon intracellular activation, β-lapa undergoes NQO1-mediated redox cycling to generate H₂O₂, which is further converted into ·OH through ferrocene-catalyzed Fenton reactions. Meanwhile, arginine-derived nitric oxide (NO) reacts with ROS intermediates to form highly reactive peroxynitrite (ONOO⁻), thereby amplifying oxidative damage and extending the effective range of redox stress. In addition, NO-mediated vascular remodeling alleviates tumor hypoxia and enhances intratumoral drug accumulation. Consequently, the HFSAL nano-prodrug effectively induces synergistic ferroptosis and apoptosis, leading to significant tumor growth inhibition and metastasis suppression in vivo with favorable biosafety. This work presents a redox-amplifying nano-prodrug strategy that exploits NQO1-associated metabolic vulnerability to enhance ferroptosis-based cancer therapy. Graphical

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ACS Applied Materials & Interfaces · 2024 · IF 8.3

NIR-Mediated Pyroelectric Catalysis for Sustained ROS/RNS Generation and Advanced Cancer Therapy In Vivo via Injectable Hydrogel

Yandai Lin,Yanxi Yang,Xueli Ren,Zhe Liu

Exogenous electrical stimulation has attracted considerable attention due to the advantages of microelectric induction and subsequent biological effects such as actin reorganization and reactive oxygen species (ROS) generation. Herein, an injectable hydrogel of BPR-ARG@Gel (BAG) with pyroelectric BPR nanoparticle loading and l-arginine (ARG) introduction was fabricated for advanced cancer therapy in vivo. Due to the photothermal effect, the holes and electrons in BPR nanoparticles were separated to produce an open-circuit voltage and consequently catalyze water H2O to generate toxic superoxide (•O2–) and hydroxyl radicals (•OH). These ROS substances further oxidize ARG to produce NO for synergistic tumor treatments. The mice experiments indicated that the employment of BAG hydrogel incorporation with a near-infrared laser downregulated the heat shock protein and recruited immune cells with 5-fold-enhanced expression of proinflammatory cytokines of interferon-γ. It was also noteworthy that the injectable hydrogel of BAG substantially induced the generation of reactive oxygen/nitrogen species (ROS/RNS) with reliable biosafety and strong tumor inhibition. Overall, these findings have provided potentially new inspirations and a feasible strategy to translate this multifunctional hydrogel toward tumor therapy in a pyroelectric stimulation manner.

CAS / MDL: 74-79-3 1401-55-4
研究领域: 癌症治疗 · 材料科学 · 生物医学工程 · 纳米技术 · 免疫疗法
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VIEW · 2026 · IF 8.1

Tumor cell membrane camouflaged liposomal pharmaceuticals for cascade catalysis-driven redox modulation and synergistic ROS/RNS antitumor therapy

Guangrong Zheng,Tengfei Ke,Hongjin Wang,Hong Huang,Ying Zhang,Guanghai Fei,Chengde Liao,Haiyan Yang

The antioxidant defense system (ADS) within the tumor microenvironment restricts the efficacy of reactive oxygen species (ROS) based therapies by conferring intrinsic redox tolerance. To overcome this limitation, we develop a tumor cell membrane camouflaged liposomal nanoplatform (C-MLip@LA) that modulates the ADS to enhance tumor-targeted therapy through a synergistic reactive oxygen/nitrogen species (ROS/RNS) cascade. The system encapsulates L-arginine (LA) as the core, anchors MnO 2 nanoparticles on the liposomal surface, and is cloaked with homologous tumor cell membranes, thereby enabling tumor-specific recognition and immune evasion. C-MLip@LA disassembles after cellular internalization, where MnO 2 depletes intracellular glutathione (GSH) and is reduced to Mn 2 + , thereby elevating ROS levels and enabling T 1 -weighted magnetic resonance imaging. Concurrently, the released LA reacts with endogenous H 2 O 2 to generate nitric oxide (NO). The interplay between NO and ROS initiates a cascade reaction that produces highly cytotoxic peroxynitrite, thereby amplifying immunogenic cell death and leading to pronounced tumor growth inhibition in a CT-2A tumor model. Collectively, this work presents a biomimetic nanoplatform for redox-modulated cancer therapy with integrated diagnostic and immunomodulatory functions.

CAS / MDL: 92614-59-0
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CHEMICAL ENGINEERING JOURNAL · 2023 · IF 15.1

An injectable selenite-containing hydrogel for synergistic tumor therapy by triggering ROS/RNS generation and disrupting NADPH homeostasis

Weiyong Tao,Xiaodan Wu,Jiaqi Li,Feige Wu,Chen Chen,Ting Jiang,Cunjing Xu,Shangtong Jiang,Jianglin Wang,Bo Xiao,Yingying Du,Shengmin Zhang

The anti-cancer effect of selenite (SeO 3 2− ) is limited by its short half-life and narrow therapeutic window. Peroxynitrite (ONOO − ), the most active reactive nitrogen species (RNS) derived from nitric oxide (NO) reacting with superoxide anion (O 2 •− ), is still not fully exploited in the combination therapy against cancers. Herein, an injectable hydrogel is developed to trigger intracellular reactive oxygen species (ROS)/RNS bursts and disrupt nicotinamide adenine dinucleotide phosphate (NADPH) homeostasis via an innovative SeO 3 2− -based strategy. Calcium selenite/ L -Arginine ( L -Arg) nanospheres (SL NPs) are synthesized as the donor of NO and SeO 3 2− . The injectable Alg@SLGA sol composed of SL NPs, glucose oxidase (GOx), 6-aminonicotinamide (6-AN, an inhibitor of the pentose phosphate pathway (PPP)), and sodium alginate (Alg) can convert to gel in a physiological environment. Peritumoral injection of Alg@SLGA hydrogel is performed for safe and targeted treatment. The loaded GOx catalyzes glucose oxidation to produce acidic H 2 O 2 , initiating the release of NO and SeO 3 2− from Alg@SLGA. SeO 3 2− reacts with intracellular GSH and H 2 O 2 to generate •OH and O 2 •− , which further interacts with NO to form ONOO − . The SeO 3 2− and 6-AN synergistically trigger intracellular NADPH exhaustion by promoting cystine metabolism-mediated NADPH consumption and inhibiting NADPH generation, respectively. Moreover, Alg@SLGA effectively induces immunogenic cell death (ICD) of tumor cells, further provoking systemic antitumor immune responses. As a consequence, the injectable Alg@SLGA hydrogel achieves enhanced ROS/RNS-mediated combination therapy by synergistically disrupting NADPH homeostasis and improving antitumor immunity.

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APPLIED CATALYSIS B-ENVIRONMENTAL · 2024 · IF 20.2

Nitrate promoted ATZ degradation in Z-scheme Cs3Bi2I9/BiVO4 photocatalytic system: Coupling ·OH and RNS mediated reduction and oxidation

Xinyu Duan,Huiping Jia,Tingting Cao,Hongbin Yu,Yanan Zhang,Ying Lu,Dandan Zhou

Nitrate, widely present in water, can be excited by UV light and generate reactive nitrogen species (RNS) etc., facilitating pollutants selective degradation. In this work, the promoting effect of nitrate on atrazine removal in the Z-scheme Cs 3 Bi 2 I 9 /BiVO 4 (CBI/BVO) photocatalytic system was studied. The CBI/BVO composite utilized CBI and BVO excitation to enhance photogenerated carriers production, and the Z-scheme heterojunction to increase photoinduced carriers separation yield, with a maximum value of 15.41 times that of pure BVO, releasing CBI electrons and BVO holes with powerful redox ability. Thanks to nitrate addition, the atrazine degradation improved, whose kinetic constant was 14.46 and 2.37 times higher than that of nitrate photolysis and 0.32-CBI/BVO photocatalysis . DFT , HPLC-MS, EPR , and toxicity assessments indicated the electron rich portion of atrazine and its intermediates were susceptible to RNS attack and underwent dechlorination , that combined with the oxidation brought by ·OH, synergistically promoting atrazine degradation, mineralization, and detoxification.

研究领域: 环境科学 · 光催化技术 · 污染控制 · 材料科学
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CHEMICAL ENGINEERING JOURNAL · 2023 · IF 15.1

Remediation of polychlorinated biphenyls (PCBs) polluted soil using dielectric barrier discharge (DBD) plasma: Reactive nitrogen species (RNS) and produced dioxins

Jingyi Zhao,Ai Zhang,Yinyin Zhang,Paul Héroux,Luxiang Zhu,Xiang Li,Pan Li,Yanan Liu

Soil contaminated by PCBs from the electronic processing industries has attracted global concern because of their potentially persistent risks to human and ecological health. In this study, remediation of PCBs polluted soil using dielectric barrier discharge plasma (DBD) focused on 3,3′,4,4′-tetrachlorobiphenyl (PCB77) and 2,2′-dichlorobiphenyl (PCB4). About 90 % of PCB77 and PCB4 were degraded under input power of 120 W within 30 min. The carbon dioxide mineralization of PCB77 achieved at 18.2 % in 10 min treatment. Greater PCBs degradation was obtained with higher input power, lower moisture content, weaker acidity and presence of oxygenated gas. Increasing initial concentration of PCBs had no significant effect on PCB77 degradation, but contributed to PCB4 removal. PCBs degradation reactions were initiated by high-energy electrons. Reactive oxygen species (ROS) played major roles in PCBs degradation, which was also promoted by reactive nitrogen species (RNS) such as peroxynitrous radicals (HOONO). Multiple spectroscopies showed that chlorine radicals participated in PCBs degradation reactions. Chlorine substitution, ring-opening and bridge cleavage reactions were the main degradation pathways for PCB77. The production and re-degradation of trace dioxin-like substances ensured the safety of DBD use in the remediation of PCBs-contaminated soils.

CAS / MDL: 13029-08-8 32598-13-3
研究领域: 环境科学 · 污染治理
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