CHEMICO-BIOLOGICAL INTERACTIONS
·
2024
·
IF 4.7
Yan-Ting Lv,Tian-Bin Liu,Yue Li,Zhen-Yong Wang,Cai-Yu Lian,Lin Wang
Cadmium (Cd), a prevalent environmental contaminant, has attracted widespread attention due to its serious health hazards. Ferroptosis is a form of iron-dependent oxidative cell death that contributes to the development of various kidney diseases. However, the mechanisms underlying the occurrence of ferroptosis in Cd-induced renal tubular epithelial cells (TECs) have not been fully elucidated. Hereby, both in-vitro and in-vivo experiments were established to elucidate this issue. In this study, we found that Cd elicited accumulation of lipid peroxides due to intracellular ferrous ion (Fe 2+ ) overload and glutathione depletion, contributing to ferroptosis. Inhibition of ferroptosis via chelation of Fe 2+ or reduction of lipid peroxidation can significantly mitigate Cd-induced cytotoxicity. Renal transcriptome analysis revealed that the activation of heme oxygenase 1 (HO-1) was closely related to ferroptosis in Cd-induced TECs injury . Cd-induced ferroptosis and resultant TECs injury are significantly alleviated due to HO-1 inhibition, demonstrating the crucial role of HO-1 in Cd-triggered ferroptosis. Further studies showed that accumulation of lipid peroxides due to iron overload and mitochondrial ROS (mtROS) generation was responsible for HO-1-triggered ferroptosis in Cd-induced cytotoxicity. In conclusion, the current study demonstrates that excessively upregulating HO-1 promotes iron overload and mtROS overproduction to trigger ferroptosis in Cd-induced TECs injury, highlighting that targeting HO-1-mediated ferroptosis may provide new ideas for preventing Cd-induced nephrotoxicity .
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ADVANCED FUNCTIONAL MATERIALS
·
2024
·
IF 18.5
Hao Cheng,Yongqiang Yang,Yueyue Wang,Jiqiang Guo,Xiong Jiao,Di Huang,Meiwen An,Xiaohong Yao,Paul K. Chu,Xiangyu Zhang
The hypoxic environment of deep tissue and the weak energy of microwave (MW) are still the major limitations of MW catalytic therapy. In this work, an MW-responsive nano-platform consisting of an Mn-doped porphyrin metal–organic framework loaded with calcium peroxide (Mn 0.1 PCC) is designed to regulate the microenvironment of the injection site and enhance the generation of reactive oxygen species. The excellent MW absorbing properties of Mn 0.1 PCC improve the Fenton reaction between hydrogen peroxide formed by the hydrolysis of calcium peroxide and released Mn 2+ generating more hydroxyl radicals under MW. This process does not consume the oxygen substrate and even produces oxygen to improve the hypoxic environment. Therefore, at a low and safe concentration (125 µg mL −1 ), the antibacterial rate of Mn 0.1 PCC against 4 × 10 8 CFU mL −1 of methicillin-resistant Staphylococcus aureus (MRSA) after MW irradiation for 15 min is 99.71% ± 0.18%. Mn 0.1 PCC, upon exposure to MW, prevents the recurrence of bacterial infections and overcomes drug resistance by inhibiting quorum sensing and the two-component system of MRSA. It can also induce macrophage M1 polarization, up-regulate the pro-inflammatory factor tumor necrosis factor-α, and enhance the phagocytosis of macrophage to bacteria. This strategy provides insights into the development of high-performance MW-responsive nanocomposites for the treatment of infections in deep tissues.
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BIOMACROMOLECULES
·
2025
·
IF 5.4
Yehao Chen,Bo Yuan,Zhixuan Yang,Shifeng Yan,Kaixuan Ren,Qingmeng Pi,Yan Liu,Jingbo Yin
High levels of reactive oxygen species (ROS) and hypoxia in diabetic wounds significantly hinder the healing process. In this work, a kind of catalase-like nanozyme-hybrid hydrogel was developed to explore the potential of harnessing endogenous excessive ROS as an oxygen source to synergistically regulate oxidative stress and hypoxia, thereby enhancing diabetic wound healing. The hydrogels exhibited rapid degradation and controlled release of ferrihydrite nanozymes in response to oxidative stress, which continuously catalyzed the decomposition of H2O2 to generate oxygen, effectively scavenging ROS and reducing the risk of local oxygen toxicity. The hydrogels relieved intracellular oxidative stress and the hypoxic microenvironment simultaneously in vitro. The hydrogel dressings effectively inhibited oxidative damage at wound sites, promoted epidermis formation and collagen deposition, and significantly accelerated wound healing in db/db mice. Therefore, the catalase-like nanozyme-hybrid hydrogels represent a promising strategy for diabetic wound dressings, addressing both oxidative stress and hypoxia to improve healing outcomes.
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ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Lin Liu,Shimiao Wu,Jingya Xiu,Yang Liu,Bingrong Hong,Yihong Peng,Lingao Yin,Yilin Song,Ziqi Li,Ziyun Lin,Degong Yang,Chunrong Yang
The myocardial ischemia-reperfusion injury (MIRI) is an acute and serious disease with complex pathogenesis, which is intricately associated with oxidative stress, calcium overload, and inflammation. Currently, widely utilized antioxidant or anti-inflammatory strategies present challenges in effectively reversing tissue damage. In this study, a biomimetic targeted mesoporous polydopamine nanoparticle (MR/B@PM) loaded with rapamycin (RAPA) and calcium chelating agent (BAPTA-AM) was successfully constructed, and precise delivery was achieved by a platelet membrane (PM). MR/B@PM facilitated targeted delivery to cardiomyocytes (26-fold) and enhanced intracellular uptake (1.75-fold) compared to MR/B, which was mainly attributed to the natural infarct homing ability of PM and the high affinity between PM and myocardial cells. MR/B@PM significantly inhibited 85.78% of hypoxia-reoxygenation (H/R)-induced cell apoptosis and exerted favorable inhibitory effects on myocardial injury with reduced CK-MB and LDH to 7.61 and 19.43 pg/mL compared to the H/R group. It was proved that MPDA acted as a combined effect with BAPTA-AM and RAPA to inhibit cardiomyocyte apoptosis and modulate the inflammatory response by scavenging ROS and reducing calcium overload. And in the MIRI rat model, MR/B@PM has been demonstrated to significantly reduce serum levels of CK-MB and LDH, while effectively suppressing inflammatory responses. Notably, MR/B@PM effectively reduced infarct size to 19.51% and prevented cardiac remodeling caused by MIRI. This designed nanoplatform comprehensively regulated the multiple pathogenesis of MIRI, which provided an effective strategy and mechanism for the treatment of MIRI.
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BIOMATERIALS
·
2025
·
IF 12.9
Xinrong Zou,Xinyao Fan,Ping Xu,Xiufeng Yu,Chan Luo,Zhuxi Kang,Xin Shen,Jiaoni Zheng,Jisheng Wang,Baicheng He,Zeng Tu,Xiaoming Fu,Yongbo Peng
Diabetes mellitus (DM) aggravates periodontitis due to disordered glucose metabolism, leading to accelerated bone destruction and increasing dental plaque reproduction to induce local inflammation. The hyperglycemic state of DM leads to reactive oxygen species (ROS) overproduction that inhibits osteogenic differentiation in periodontal. These make a great challenge for the treatment of diabetic periodontitis. ROS-scavenging materials with additional anti-inflammation and anti-bacterial properties are highly sought after for the treatment of diabetic periodontitis. Herein, we have prepared the selenium-albumin corona rinse (H@Se NPs) through the albumin/nano-Se assembly strategy. H@Se NPs have better anti-inflammation via promoting the polarization of macrophages from the M1 to M2 phenotype and anti-bacterial effects than the commercially available selenium nanoparticles (Se NPs). Additionally, H@Se NPs can scavenge ROS to modulate the periodontal osteogenic microenvironment, a mechanism that involves regulating thioredoxin reductase 1 (TrxR1) synthesis and activating the TrxR1/ROS/β-catenin cascade. Furthermore, studies conducted in vivo have verified that H@Se NPs can suppress the formation of subgingival microbial colonies while enhancing osteogenic differentiation in diabetic pathological environments and improving periodontal bone regeneration via ROS scavenging. Collectively, these findings unveil new therapeutic paradigms for the clinical management of diabetic periodontitis.
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MATERIALS & DESIGN
·
2021
·
IF 7.991
Zhanxia Zhang,Yongqing Heng,Wei Cheng,Yongfu Pan,Shuaishuai Ni,Hegen Li
Knocking down the UBC12 with siRNA could significantly suppress the Neddylation pathway and result in an admirable anti-cancer effect. However, how to transport siRNA in vivo with low potential toxicity is an urgent problem to be solved. For enhancing bioavailability of siRNA, folic acid (FA)-modified PLGA (poly(lactic- co -glycolic acid))-TK (thioketal)-PEG (polyethylene glycol) nanomedicine was designed for siRNA delivery. The nano-vector possesses spherical morphology and admirable biocompatibility. After targeted endocytosis through the selective recognition between FA and its receptor in liver cancer cells, the genetic nanomedicine was triggered by high ROS level and released its cargo siRNA in tumor microenvironment. In vitro and In vivo results revealed that the genetic nanomedicine not only inhibits proliferation and promotes apoptosis of liver cancer cells, but also possesses excellent therapeutic efficacy by knowing down UBC12 and suppressing the Neddylation pathway as well as accumulating tumor-suppressive CRL substrates. Consequently, this work provides a novel approach to construct a biodegradable nanomedicine with targeted recognition and smart response. Moreover, it inhibits the viability of liver cancer cells with high efficiency and low potential toxicity. Importantly, the PLGA nanomedicine demonstrates the encouraging potential for multifunctional nano-system applicable for cancer therapy.
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JOURNAL OF ENVIRONMENTAL MANAGEMENT
·
2026
·
IF 9.2
Siyuan Zheng,Bolin Li,Jun Wang,Shanshan Huang,Simiao Wu,Zihang Wang,Guoliang Bai
Levofloxacin (LEV) residues in water are refractory and ecotoxic, while heterogeneous catalytic ozonation (HCO) systems suffer from limited efficiency and insufficient anti-interference ability. To address this, a composite catalyst, Co–Mn/CTS@NZ, was fabricated by loading Co–Mn bimetallic oxides onto chitosan-modified natural zeolite through wet impregnation–calcination to target non-radical reactive oxygen species (ROS) regulation in HCO for enhanced LEV degradation and anti-interference. Under the optimized conditions (LEV 30 mg/L, O 3 5 mg/L, catalyst 5 g, pH 6.5), the system achieved 99.55% LEV removal and 55.52% mineralization in 60 min, outperforming single ozonation significantly. The catalyst exhibited excellent anti-interference performance and operated efficiently across various real water matrices, with negligible metal leaching. Quenching experiments and electron paramagnetic resonance confirmed that 1 O 2 was the primary ROS, with ·O 2 − and ·OH acting as supplementary radicals. Characterization revealed that abundant oxygen vacancies, metal valence cycles, and surface hydroxyl groups synergistically promoted ozone activation and targeted ROS generation. This study provides a low-cost, high-efficiency catalyst for LEV-contaminated water treatment and offers a theoretical basis for targeted ROS regulation in HCO technology—breaking the reliance of traditional HCO on ·OH and advancing the practical application of advanced oxidation in antibiotic pollution control.
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Advanced Science
·
2025
·
IF 14.1
Chenyang Ye,Mi Mi,Saimeng Shi,Lina Qi,Shanshan Weng,Lu Wang,Yier Lu,Chao Chen,Yinuo Tan,Mengyuan Yang,Cheng Guo,Rui Bai,Xuefeng Fang,Ji Wang,Ying Yuan
Targeting Nampt to modulate NAD + metabolism and exert antitumor effects has become a research hotspot in the field of cancer metabolism. But early clinical trials have only achieved modest results, primarily due to the need for improved efficacy and the occurrence of severe systemic adverse effects. Therefore, enhancing antitumor efficacy and reducing the adverse effects of Nampt inhibitors are urgent challenges. The research reveals that the Nampt inhibitor FK866 can induce ferroptosis in colorectal cancer cells via the NAD + /Stat3/Gpx4 signaling axis. Furthermore, the combination of FK866 and the Stat3 inhibitor C188-9 demonstrates a strong synergistic antitumor effect. Importantly, a reactive oxygen species (ROS)-responsive hydrogel that encapsulates FK866 and C188-9 for in situ drug delivery, effectively reducing systemic side effects, is developed. Intriguingly, mass cytometry time-of-flight (CyTOF) analysis indicates that the combined treatment with FK866 and C188-9 exerts antitumor effects by increasing the infiltration of CD8 + T cells and neutrophils into the tumor, as well as enhancing the expression of immune-regulatory molecules, including IFN-γ, IL-10, and perforin. Thus, this localized treatment not only minimizes systemic adverse effects, but also markedly amplifies antitumor efficacy through the modulation of both tumor cells and the tumor immune microenvironment, representing a promising antitumor treatment strategy.
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BIOLOGICAL TRACE ELEMENT RESEARCH
·
2026
·
IF 4.3
Yang Wenyan,Ma Lu,Hu Ting,Zhang Lei,Wu Kewei,Chen Hualin,Zhang Dandan,Luo Peng
Geochemical fluoride pollution is a global public health issue affecting a wide range and large population. The major health hazard from long-term fluoride exposure is skeletal fluorosis, a highly disabling and irreversible bone damage disease with no effective early interventions available to date. Given reactive oxygen species (ROS) accumulation is a key event in fluoride-induced bone damage, we established a sodium fluoride-exposed rat model. During the phase when fluoride induced ROS accumulation and mild bone damage in rat bone tissue, we administered Rosa roxburghii Tratt juice (RRTJ)—a natural food-medicinal homologous plant with antioxidant properties—to explore its intervention effect and potential mechanism against fluoride-induced bone damage. Results showed RRTJ inhibited fluoride-induced decreases in bone mineral density and trabecular number in male rats. Since enhanced bone resorption mediated by osteoclast overactivation is the initiating link of these fluoride-induced pathological changes, this study further found RRTJ suppressed fluoride-induced increases in osteoclast activity in male rat bone tissue, specifically reducing osteoclast numbers in bone tissue and lowering serum levels of bone resorption markers CTX and TRAP-5b. This effect is achieved by RRTJ scavenging fluoride-induced ROS accumulation in bone tissue, restoring ROS/TNF-α/NF-κB pathway homeostasis, and thereby inhibiting the overexpression of osteoclast activation-related genes tartrate-resistant acid phosphatase and cathepsin K. In conclusion, this study confirms RRT inhibits fluoride exposure-induced bone damage in male rats by regulating ROS/TNF-α/NF-κB pathway homeostasis. These findings provide new perspectives on the mechanism of fluoride-induced bone damage and, more importantly, reveal a potential novel intervention strategy.
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高影响因子
Nanoscale
·
2022
·Vol. 15
·期 1
·237-247
·
IF 8.307
Panli Han,Lianxue Zhang,Yaqi Fu,Youyu Fu,Jianxiang Huang,Jinlin He,Peihong Ni,Taimoor Khan,Yang Jiao,Zaixing Yang,Ruhong Zhou
The selective anti-tumor activity and less toxic nature of hypoxia-activated prodrugs including tirapazamine (TPZ) are harbored by hypoxia levels in tumors, the inadequacy of which leads to failure in clinical trials. Thus, the development of effective clinical applications of TPZ requires advanced strategies to intensify hypoxia levels in tumors effectively and safely. In this study, we designed and fabricated a paclitaxel (PTX)-loaded dual-response delivery system with a low dose (e.g., 2 Gy) of X-ray and reactive oxygen species on the basis of diselenide block copolymers. Upon the external X-ray stimulus, the system accurately released encapsulated PTX at tumor sites and remarkably improved tumor hypoxia levels by causing severe damage to tumor blood vessels. Subsequently, these enhanced tumor hypoxia levels effectively activated the reduction of TPZ into benzotriazinyl free radicals, which significantly improved the antitumor efficacy of our system against 4T1 breast cancer cells with an initial tumor volume of 500 mm3. Moreover, the dual-stimulus coordinated and controlled release of PTX was found to largely avoid the off-target effects of PTX on normal cells while exhibiting very limited side effects in experimental mice. The current novel strategy for regulating tumor hypoxia levels offers an effective and safe way to activate TPZ for the treatment of large solid tumors.
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Acta Biomaterialia
·
2022
·
IF 10.633
Mengying Hou,Xuejie Wu,Ziyin Zhao,Qiurong Deng,Yongbing Chen,Lichen Yin
Neutrophils serve as a key contributor to the pathophysiology of myocardial ischemia reperfusion injury (MIRI), because the unregulated activation and infiltration of neutrophils lead to overwhelming inflammation in the myocardium to cause tissue damage. Herein, endothelial cell-targeting and reactive oxygen species (ROS)-ultrasensitive nanocomplexes (NCs) were developed to mediate efficient co-delivery of VCAM-1 siRNA (siVCAM-1) and dexamethasone (DXM), which cooperatively inhibited neutrophil recruitment by impeding neutrophil migration and adhesion. RPPT was first synthesized via crosslinking of PEI 600 with ditellurium followed by modification with PEG and the endothelial cell-targeting peptide cRGD. RPPT was allowed to envelope the DXM-loaded PLGA nanoparticles and condense the siVCAM-1. After systemic administration in rats experiencing MIRI, the cRGD-modified NCs efficiently targeted and entered the inflamed endothelial cells, wherein RPPT was sensitively degraded by over-produced ROS to trigger intracellular siVCAM-1 release and potentiate the VCAM-1 silencing efficiency. As a consequence of the complementary function of DXM and siVCAM-1, the NCs notably mitigated neutrophil infiltration into ischemic myocardium, provoking potent anti-inflammatory efficacy to reduce MIRI and recover cardiac function. The present study offers an effective approach for the controlled co-delivery of siRNA and drug cargoes, and it also highlights the importance of multi-dimensional manipulation of neutrophils in anti-inflammatory treatment. Statement of significance The unregulated activation and infiltration of neutrophils lead to overwhelming inflammation in the myocardium after myocardial ischemia reperfusion injury (MIRI). Here, endothelial cell-targeting and ROS-ultrasensitive nanocomplexes (NCs), comprised of PLGA NPs decorated with cRGD-poly(ethylene glycol) (PEG)-modified, ditellurium-crosslinked PEI (RPPT), were developed to mediate efficient co-delivery of VCAM-1 siRNA (siVCAM-1) and dexamethasone (DXM). DXM and siVCAM-1 with complementary functions inhibited both the migration and adhesion of neutrophils, efficiently interventing the neutrophil recruitment and interrupting the self-amplified inflammation cascade in the injured myocardium. The molecular design of RPPT renders an effective example for constructing polymeric materials with high ROS sensitivity, and it resolves the critical dilemma related to polycation-mediated siRNA delivery, such as siRNA encapsulation versus release, and transfection efficiency versus toxicity.
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Frontiers in Pharmacology
·
2021
·
IF 5.811
Cao Qiongqiong,Xu Dongmei,Chen Yong,Long Yueming,Dai Fang,Gui Li,Lu Yunxia
Macrovascular disease is tightly associated with obesity-induced metabolic syndrome. Sitagliptin (SIT), an orally stable selective inhibitor of Dipeptidyl peptidase-4 (DPP-4), has protective effects on endothelium. However, the mechanisms enabling SIT to exhibit resistance to diet-induced obesity (DIO) related with reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress in the aorta and endothelial cells have not been reported yet. Therefore, the present study was conducted to determine if SIT exerts protective role in the thoracic aortas isolated from the high-fat diet (HFD)-treated rats and palmitate (PA)-treated endothelial cells by alleviating ROS and ER stress. Male Sprague Dawley rats were randomly divided into standard chow diet (SCD), HFD and HFD plus sitagliptin administration (HFD + SIT) groups. The rats of latter two groups were given HFD fodder for 12 weeks, then the HFD + SIT rats were treated with SIT (10 mg/kg/d) by intragastric administration for another 8 weeks. The body mass, vascular tension, serum oxidative stress indices and inflammatory parameters, pathological changes, protein expression of endothelial nitric oxide synthase (eNOS), the genes associated with ER stress and apoptosis in the thoracic aorta were measured. Furthermore, cell proliferation, ROS and the protein expression associated with ER stress (especially CHOP) and apoptosis were assessed in human umbilical vein endothelial cells (HUVECs) incubated with SIT and PA. Compared to the SCD rats, the HFD rats had higher serum lipid levels, decreased vascular tension, increased inflammation, oxidative and ER stress, and apoptosis of endothelial cells. PA promoted ROS generation, ER stress and apoptosis, inhibited cell proliferation in HUVECs. SIT treatment obviously ameliorated apoptosis via alleviating ROS and ER stress in the thoracic aortas isolated from HFD-fed rats and PA-treated HUVECs. The results suggest that SIT improved endothelial function via promoting cell proliferation and alleviating ROS-ER stress-CHOP pathway both in vivo and in vitro.
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