iScience
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2023
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IF 5.8
Hao Hu,Junxu Yang,Yanping Zhong,Jiawei Wang,Jinhong Cai,Cuijuan Luo,Zhiqiang Jin,Ming Gao,Maolin He,Li Zheng
Summary Excessive reactive oxygen species (ROS) in joints could lead to gradual degeneration of the extracellular matrix (ECM) and apoptosis of chondrocytes, contributing to the occurrence and development of osteoarthritis (OA). Mimicking natural enzymes, polydopamine (PDA)-based nanozymes showed great potential in treating various inflammatory diseases. In this work, PDA loaded with ultra-small palladium (PDA-Pd) nanoparticles (NPs) was employed to scavenge ROS for OA therapy. As a result, PDA-Pd effectively declined the intracellular ROS levels and exhibited efficient antioxidative and anti-inflammatory capacity with good biocompatibility in IL-1β stimulated chondrocytes. Significantly, assisted with near-infrared (NIR) irradiation, its therapeutic effect was further enhanced. Further, NIR-stimulated PDA-Pd suppressed the progression of OA after intra-articular injection in the OA rat model. With favorable biocompatibility, PDA-Pd exhibits efficient antioxidative and anti-inflammatory capacity, leading to the alleviation of OA in rats. Our findings may provide new insights into the treatment of various ROS-induced inflammatory diseases.
研究领域:
生物医学工程
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纳米技术
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骨科
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炎症研究
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产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2024
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IF 5.3
Ming Qian,Liang Gong,Tao Jia,Hao Liu,Qichuan Jiang,Yijie Wang,Xuefeng Wang
Sonodynamic therapy (SDT) has demonstrated considerable potential in its noninvasive approach and ability to target tumors located deep within brain tissues (>10 cm). However, the effectiveness of this technique is hindered by tumor hypoxia (2% O2), the abundance of the reactive oxygen species (ROS) scavenger glutathione (GSH), and the limited ROS generation capacity of the sonosensitizer. In light of these limitations, a cascade nanozyme comprising platinum (Pt)-coated porphyrin metal–organic frameworks (PCN-224(Fe)) modified with COOH-PEG was developed [Pt/PCN-224(Fe)/PEG, labeled as PFMP nanozyme] to enhance the toxicity of ROS. This nanozyme emulates the catalytic function of Pt in the decomposition of hydrogen peroxide (H2O2) into O2 for the purpose of alleviating tumor hypoxia. Additionally, it replicates the function of glutathione peroxidase (GPX) by utilizing iron (Fe3+) to reduce the overexpression of GSH. These two mechanisms act in concert to amplify the generation of ROS. They achieve this by enhancing O2 production and impairing the capacity of GSH to scavenge ROS, thereby synergistically potentiating the toxicity of ROS. In vitro and in vivo studies have demonstrated evidence for efficient ROS generation, resulting in a significant 6-fold reduction in tumor volume compared to the control groups and achieving an impressive 80% survival rate 30 days after treatment.
研究领域:
癌症治疗
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纳米技术
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生物医学工程
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药学
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产品关联
DOI
高影响因子
Journal of Materials Chemistry B
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2019
·Vol. 7
·期 44
·6924-6933
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IF 5.047
Pei Liu,Weitao Yang,Lei Shi,Haiyan Zhang,Yan Xu,Peiru Wang,Guolong Zhang,Wei R. Chen,Bingbo Zhang,Xiuli Wang
Phototherapy, particularly photothermal therapy (PTT) and photodynamic therapy (PDT), has become a promising therapeutic technique for the treatment of skin cancers because of its minial invasiveness, high efficacy, and low side effects. Nevertheless, single modality therapy, either PTT or PDT, has limited clinical effectiveness in treating skin cancers. Thus, combined applications of PTT and PDT have been frequently reported; however, PTT and PDT often require their respective photoagents and excitation light sources, resulting in challenges in clinical transformation. In this study, to address these issues, we report the use of biocompatible gold nanoclusters Au25(Capt)18 for the concurrent PTT and PDT treatment of cutaneous squamous cell carcinoma (cSCC) using an 808 nm near-infrared (NIR) laser. Utilizing their high light-thermal conversion efficiency, potent generation of singlet oxygen, and strong photothermal stability, Au25(Capt)18 nanoclusters potentiated a significant proliferation suppression of cSCC XL50 cells in vitro and the inhibition of cSCC tumors on SKH-1 mice in vivo. In particular, under 808 nm light irradiation, the tumor-cell-killing contributions of PTT and PDT were estimated to be 28.86% and 71.14%, respectively, by using an ROS scavenger to quench the PDT effect. Tumor-infiltrating CD4+ T and CD8+ T cells were observed after one course of concurrent PTT and PDT. Preliminary toxicity studies indicated low adverse effects of the Au25(Capt)18 nanoclusters. Through this study, we report the use of a simple nanostructure for simultaneous PTT and PDT applications to effectively kill cSCC and to induce anti-tumor immune responses. Our study could lead to the development of effective photoagents for current, synergistic applications of different phototherapies with targeted immunological responses for the treatment of cancers.
研究领域:
肿瘤学
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纳米技术
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光疗
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免疫学
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产品关联
DOI
PubMed
高影响因子
Bioactive Materials
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2022
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IF 16.874
Rui Wang,Jian Lu,Jiasheng Yin,Han Chen,Hongmei Liu,Fei Xu,Tongtong Zang,Rende Xu,Chenguang Li,Yizhe Wu,Qilin Wu,Xiang Fei,Meifang Zhu,Li Shen,Junbo Ge
An increased level of reactive oxygen species (ROS) plays a major role in endothelial dysfunction and vascular smooth muscle cell (VSMC) proliferation during in-stent thrombosis and restenosis after coronary artery stenting. Herein, we report an electrospun core-shell nanofiber coloaded with 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPOL) and rapamycin (RAPA) that correspondingly serves as an ROS scavenger and VSMC inhibitor. This system has the potential to improve the biocompatibility of current drug-eluting stent (DES) coatings with the long-term and continuous release of TEMPOL and rapamycin. Moreover, the RAPA/TEMPOL-loaded membrane selectively inhibited the proliferation of VSMCs while sparing endothelial cells (ECs). This membrane demonstrated superior ROS-scavenging, anti-inflammatory and antithrombogenic effects in ECs. In addition, the membrane could maintain the contractile phenotype and mitigate platelet-derived growth factor BB (PDGF-BB)-induced proliferation of VSMCs. In vivo results further revealed that the RAPA/TEMPOL-loaded covered stents promoted rapid restoration of vascular endothelium compared with DES and persistently impeded inflammation and neointimal hyperplasia in porcine models.
研究领域:
生物医学工程
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药学
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心脏病学
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材料科学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2024
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IF 6.9
Rongrong Luo,Jingjing Su,Wenying Zhang,Wenguang Huang,Qianqian Zhou,Pengchao Sun,Yongxing Zhao
Rheumatoid arthritis (RA) is characterized by high level of reactive oxygen species (ROS) and proinflammatory cytokines, which facilitate the activation of the inflammatory signaling such as NF-κB pathway and exacerbate the development of inflammation. Herein, we designed a nanodrug by encapsulating the NO donor S-nitrosoglutathione (GSNO) into an emulsion and coating the surface with a polydopamine (PDA) layer to yield GSNO@PDA, which simultaneously scavenged the extra ROS and suppressed NF-κB signaling for potent RA treatment. To enhance the cellular uptake and NO generation efficiency, dextran sulfate (DS) and Cu 2+ were anchored on the surface of GSNO@PDA to obtain the final formulation GSNO@PDA@DS. Our results demonstrated that GSNO@PDA@DS were successfully prepared and the modification of DS effectively boosted the cellular uptake of GSNO@PDA@DS. Moreover, GSNO@PDA@DS lowered cellular ROS and elevated intracellular NO, resulting in a decrease of M1 phenotype, inhibition of NF-κB pathway and down-regulation of proinflammatory cytokine tumor necrosis factor-α (TNF-α). Further in vivo studies confirmed that GSNO@PDA@DS significantly relieved symptoms and bone erosion by regulating the microenvironment of RA, highlighting the potential of GSNO@PDA@DS for RA therapy through ROS scavenging and NO-mediated suppression of inflammatory signaling.
研究领域:
药理学
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纳米技术
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炎症生物学
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风湿病学
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产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
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2024
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IF 3.8
Dan Song,Yuan Liu,Kehui Wu,Manting Lyu,Yongshu Wu,Yanan Zhang,Panling Wang,Xiangchen Li
The present study sought to investigate the protective effect of Lycopene (LYC) on Bisphenol A (BPA)-induced lipid accumulation and elucidate the potential molecular mechanism. In vitro, the PK15 cells with or without LYC were exposed to BPA for 6 h to detect the lipid accumulation using Nile red’s and Oil Red O’ staining. Meanwhile, redox status, mitochondrial function, gene expression and protein levels relating to lipid accumulation were evaluated by cellular biochemical assays, immunofluorescence staining, quantitative real-time PCR (qRT-PCR) and Western blot, respectively. In addition, ROS scavenger N-acetylcysteine (NAC), SIRT1 inhibitor EX527, SIRT1 siRNA and PGC-1α siRNA were used to verify the target signaling pathways responsible for the protective effect of LYC against BPA-indcued lipid accumulation. In vivo, the twenty four male Wistar rats were randomly divided into three groups, received either BPA (50 mg/kg/day BW) or LYC (10 mg/kg/day BW) orally for 60 days. The kidney tissues were evaluated by HE’s and Oil Red O’s staining, lipid-associated genes and proteins expression were detected through qRT-PCR and Western blot. The results showed that BPA-exposed PK15 cells and rats had increased lipid droplets with elevated transcription of lipogenic factors SREBP1 and PPARγ, and down-regulated PPARα expression, and which is accompanied by redox imbalance and abnormal mitochondrial function. Conversely, LYC prevented BPA-induced lipid metabolism disorder and lipid accumulation through impeding ROS overproduction. Moreover, PK15 cells and rats exposed to BPA showed decrease in SIRT1 and PGC-1α levels, whereas LYC blocked the decrease of SIRT1 and PGC-1α protein levels. Furthermore, inhibition or silence of SIRT1 and PGC-1α abrogated the improvements of LYC on ROS generation, mitochondrial mass impairement and lipid accumulation in BPA-treated PK15 cells. Collectively, these findings indicate that SIRT1/PGC-1α signaling pathway is involved in the protective effect of LYC on BPA-induced lipid accumulation. These results also provide a potential promising therapeutic of LYC against BPA-induced lipid accumulation in kidney cells and organs.
研究领域:
药理学
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细胞生物学
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分子生物学
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毒理学
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产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2024
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IF 10.5
Yanjuan Huang,Xiuling Dai,Yujun Gong,Lingling Ren,Yong Luo,Yue Sun,Meixu Chen,Jingwen Jiang,Zilin Guan,Chunshun Zhao
Postoperative abdominal adhesions are a common clinical problem after surgery and can cause many serious complications. Current most commonly used antiadhesion products are less effective due to their short residence time and focus primary on barrier function. Herein, we developed a sprayable hydrogel barrier (sHA-ADH/OHA-E) with self-regulated drug release based on ROS levels at the trauma site, to serve as a smart inflammatory microenvironment modulator and GATA6 + macrophages trap for non-adherent recovery from abdominal surgery. Sulfonated hyaluronic acid (HA) conjugates modified with adipic dihydrazide (sHA-ADH), and oxidized HA conjugates grafted with epigallocatechin-3-gallate (EGCG) via ROS-cleavable boronate bonds (OHA-E) were synthesized. sHA-ADH/OHA-E hydrogel was facilely fabricated within 5 s after simply mixing sHA-ADH and OHA-E through forming dynamic covalent acylhydrazones. With good biocompatibility, appropriate mechanical strength, tunable shear-thinning, self-healing, asymmetric adhesion, and reasonable in vivo retention time, sHA-ADH/OHA-E hydrogel meets the requirements of a perfect physical barrier. Intriguingly, sulfonic acid groups endowed the hydrogel with satisfactory anti-fibroblast and macrophage attachment capability, and were demonstrated for the first time to act as polyanion traps to prevent GATA6 + macrophages aggregation. Importantly, EGCG could be intelligently released by ROS triggering to alleviate oxidative stress and promote proinflammatory M1 macrophage polarize to antiinflammatory M2 phenotype. Further, the fibrinolytic system balance was restored to reduce fibrosis. Thanks to the above advantages, the sHA-ADH/OHA-E hydrogel exhibited excellent anti-adhesion effects in a rat sidewall defect–cecum abrasion model and is expected to be a promising and clinically translatable antiadhesion barrier.
研究领域:
生物医学工程
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药学
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组织工程
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外科研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
OncoTargets and Therapy
·
2019
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IF 3.046
Zheng-Hong Liu,Cheng-Xi Yang,Lei Zhang,Cong-Ying Yang,Xiu-Quan Xu
Background Baicalein, a natural flavonoid derived from traditional Chinese herb Scutellaria baicalensis Georg (known as Huang Qin in Chinese), has been reported to exhibit notable antitumor activity in various cancer cells, including breast cancer. However, the detailed mechanisms underlying its induced apoptosis as a prooxidant in breast cancer cells are still unknown. Materials and methods In this study, we investigated the effect of endogenous copper on cytotoxic activity of baicalin against human breast cancer MCF-7 cells in vitro. Results Baicalein could remarkably reduce the cell viability in both dose- and time-dependent manners in MCF-7 cells but with lower cytotoxic effects on normal breast epithelial cells, MCF-10A. Such cell death could be prevented by pretreatment with Cu (I)-specific chelator neocuproine (Neo) and reactive oxygen species (ROS) scavengers. Meanwhile, baicalein could induce MCF-7 cell morphological changes, promote apoptotic cell death and increase the apoptotic cell number. Moreover, DCHF-DA staining, flow cytometry and Western blotting analyses proved that baicalein triggered the mitochondrial-dependent apoptotic pathway, as indicated by enhancement the level of intracellular ROS, disruption of mitochondrial membrane potential (ΔΨm), downregulation of anti-apoptotic protein Bcl-2, upregulation of pro-apoptotic protein Bax, release of cytochrome C and activation of caspase-9 and caspase-3 in MCF-7 cells. The pretreatment with Neo remarkably weakened these effects of baicalein. Furthermore, we confirmed that the prooxidant action of baicalein involved the direct production of hydroxyl radicals through redox recycling of copper ions. Conclusion These findings suggested that baicalein, acting as a prooxidant, could trigger apoptosis in MCF-7 cells occurs via the ROS-mediated intrinsic mitochondria-dependent pathway.
研究领域:
肿瘤学
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药理学
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细胞生物学
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）