BIOMATERIALS
·
2022
·
IF 15.304
Lei Cao,Huixiang Tian,Man Fang,Zhe Xu,Dongsheng Tang,Juan Chen,Jiye Yin,Haihua Xiao,Kun Shang,Hongbin Han,Xiangping Li
cGAS-STING pathway, as an essential intracellular immune response pathway, has attracted much attention in tumor immunotherapy. However, low metabolic stability of conventional STING agonists limits their clinical application. Recent study shows that chemotherapeutic drugs cisplatin and camptothecin (CPT) can activate cGAS-STING pathway and induce immune response by DNA damage. Nevertheless, the ability of chemotherapeutic drugs to activate STING is so weak that new strategies are required to improve drug delivery efficiency for enhanced DNA damage, and then efficiently activate cGAS-STING pathway. Herein, we have developed a hybrid platinum prodrug (CPT-Pt (IV)) which can be triggered to release cisplatin and CPT in tumor cells. CPT-Pt (IV) with high hydrophobicity is further self-assembled with a ROS sensitive polymer (P1) and mPEG 2k -DSPE into ROS responsive nanoparticles (NPs). NPs could accumulate in the tumor site to release cisplatin and CPT, resulting in DNA double damage and finally activating cGAS-STING pathway, inducing DC cells maturation and increasing tumor infiltration of CD8 + T cells on colorectal cancer mouse model. This study showed that common DNA targeted drugs can activate the cGAS-STING pathway in situ via nano delivery system, and enhance the effect of chemotherapy and immunotherapy, which provide a new strategy for clinical antitumor therapy.
研究领域:
肿瘤学
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药学
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免疫学
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纳米技术
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产品关联
DOI
PubMed
高影响因子
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
·
2023
·
IF 3.9
Mengyuan Zhou,Jingchao Qiang,Jiajie Gan,Xuhui Xu,Xing Li,Shuai Zhang,Baoshi Xu,Zibo Dong
One of the most often used insecticides is Avermectin (AVM), which is toxic to aquatic organisms. Quercetin (Que) is a fruit and vegetable rich flavonoid with antioxidant activity. Fish gills are the most important respiratory organ. Carp is a biological model for studying environmental toxicology. To better understand the mechanism by which Que reduces AVM-induced gill damage in carp, we created a carp model with AVM and Que supplementation. In this study, four groups were created: the Control group, the Que group (400 mg/kg), the AVM group (2.404 μg/L), and the Que plus AVM group. The analytical methods used in this study were pathological structure examination, QPCR, Reactive Oxygen Species (ROS) and Western blot. The results showed that Que alleviated AVM-induced oxidative stress, inflammatory damage and apoptosis in the gill tissues of carp by activating the Nrf2 pathway. The mechanism was that Que alleviated the accumulation of ROS, reduced the balance between oxidation and antioxidant disrupted by AVM exposure, lowered the content of lipid peroxidation product malondialdehyde (MDA), and increased the content of antioxidant enzymes glutathione (GSH) and catalase (CAT). The Nrf2 pathway was activated. Meanwhile, Que inhibited apoptosis in the gills of carp by decreasing the levels of Bax, Cytochrome C(Cytoc), Caspase9, Cleaved-Caspase3, and elevating Bax. This is significant for future studies on Que and AVM. New recommendations are provided to reduce the threat of pollution in the water environment.
研究领域:
环境毒理学
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水生生物学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
Frontiers in Nutrition
·
2022
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IF 6.59
Xiaoxiao Xu,Chuang Ma,Hang Wu,Yuanqiao Ma,Zejin Liu,Peijie Zhong,Chaolei Jin,Wenjuan Ning,Xiao Wu,Yijie Zhang,Jichang Han,Junpeng Wang
Fructose is a commonly used food additive and has many adverse effects on human health, but it is unclear whether fructose impacts pulmonary fibrosis. TGF-β1, a potent fibrotic inducer, is produced as latent complexes by various cells, including alveolar epithelial cells, macrophages, and fibroblasts, and must be activated by many factors such as reactive oxygen species (ROS). This study explored the impact of fructose on pulmonary fibrotic phenotype and epithelial-mesenchymal transition (EMT) using lung epithelial cells (A549 or BEAS-2B) and the underlying mechanisms. Fructose promoted the cell viability of lung epithelial cells, while N-Acetyl-l-cysteine (NAC) inhibited such. Co-treatment of fructose and latent TGF-β1 could induce the fibrosis phenotype and the epithelial-mesenchymal transition (EMT)-related protein expression, increasing lung epithelial cell migration and invasion. Mechanism analysis shows that fructose dose-dependently promoted the production of total and mitochondrial ROS in A549 cells, while NAC eliminated this promotion. Notably, post-administration with NAC or SB431542 (a potent TGF-β type I receptor inhibitor) inhibited fibrosis phenotype and EMT process of lung epithelial cells co-treated with fructose and latent TGF-β1. Finally, the fibrosis phenotype and EMT-related protein expression of lung epithelial cells were mediated by the ROS-activated latent TGF-β1/Smad3 signal. This study revealed that high fructose promoted the fibrotic phenotype of human lung epithelial cells by up-regulating oxidative stress, which enabled the latent form of TGF-β1 into activated TGF-β1, which provides help and reference for the diet adjustment of healthy people and patients with fibrosis.
研究领域:
肺科学
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细胞生物学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Nano Research
·
2021
·Vol. 15
·期 2
·1455-1465
·
IF 8.897
Wen Lijuan,Peng Yu,Wang Kai,Huang Zhihua,He Shiying,Xiong Ruiwen,Wu Longping,Zhang Fengtian,Hu Fuqiang
Glioblastoma (GBM) is one of the malignant brain tumors with high mortality and no curative treatments. Abnormally elevated vascular endothelial growth factor (VEGF) in GBM seriously disrupts the blood brain barrier (BBB) with an increased permeability, resulting in poor outcome and prognosis. RNAi interference has shown strong potential to inhibit VEGF expression, thus it is necessary to development an effective and safe gene delivery system possessing the ability to cross the BBB and target GBM cells. This study aims to explore the anti-GBM effect of angiopep-2 (Ap) peptide modified reactive oxygen species (ROS) cleavable thioketal (TK) linked glycolipid-like nanocarrier (CSTKSA) delivering anti-VEGF siRNA (R), termed as Ap-CSTKSA/R complexes. Ap functionalized modification produced an enhanced cellular uptake and a stronger bio-distribution of Ap-CSTKSA/R complexes in U87 MG cells and brain tumor tissues, respectively. Ap-CSTKSA/R complexes exhibited great superiority in GBM growth inhibition and finally translated into the longest survival period mainly via receptor-mediated targeting delivery, VEGF gene silencing accompanied with remarkable angiogenesis inhibition, and suppressed expression of caveolin-1 which is involved in BBB functional regulation in the occurrence and treatment of GBM. The study indicated that Ap functionalization on ROS-responsive glycolipid-like copolymer exhibits a promising and effective gene delivery platform for GBM targeted treatment.
研究领域:
肿瘤学
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神经科学
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药学
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基因治疗
✓ 已验证
产品关联
DOI
高影响因子
DYES AND PIGMENTS
·
2023
·
IF 4.5
Yanling Xiao,Yuying Yuan,Manshan Liang,Jiahao Ni,Lichao Yu,Zu-Sheng Huang,Bing Du,Yun-Yun Quan
Fluorescence imaging-guided photodynamic therapy (PDT) is considered as an ideal alternative strategy to treat tumors. However, insufficient supply of oxygen in solid tumor tissue, aggregation-caused quenching (ACQ) of photosensitizers (PSs), poor targeting-specificity of cancer cells and short wavelengths of emission are representative obstacles for effective PDT. In this paper, three D-π-A structured PSs TSB-OH , TSBPy-OH , TSBPy-DNT with aggregation induced emission (AIE) properties and integrated type I and type II ROS generation were synthesized by modulating distinct acceptor units. Among them, TSBPy-OH is optimal with multiple advantages including near-infrared emission, good biocompatibility , remarkably intracellular ROS production ability, mitochondria targeting capability inducing cell apoptosis and enhancing PDT, and long-term tumor retention ability for imaging-guided photodynamic therapy. More importantly, efficient in vitro cancer cells damage, in vivo tumor ablation and ignorable damage in major organs during PDT are demonstrated, suggesting potential capability of TSBPy-OH in safe and effective fluorescence imaging-guided PDT. This successful example of AIE theranostics design would provide a reference for the modification of D-π-A structure organic AIEgens.
研究领域:
癌症治疗
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光动力疗法
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材料科学
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生物医学工程
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纳米技术
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
PHYTOTHERAPY RESEARCH
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2023
·
IF 7.2
Yuan Zhu,Wei-feng Yin,Pei Yu,Chao Zhang,Ming-hui Sun,Ling-yi Kong,Lei Yang
Distal metastases from breast cancer, especially bone metastases, are extremely common in the late stages of the disease and are associated with a poor prognosis. EMT is a biomarker of the early process of bone metastasis, and MMP-9 and MMP-13 are important osteoclastic activators. Previously, we found that meso-Hannokinol (HA) could significantly inhibit EMT and MMP-9 and MMP-13 expressions in breast cancer cells. On this basis, we further explored the role of HA in breast cancer bone metastasis. In vivo, we established a breast cancer bone metastasis model by intracardially injecting breast cancer cells. Intraperitoneal injections of HA significantly reduced breast cancer cell metastasis to the leg bone in mice and osteolytic lesions caused by breast cancer. In vitro, HA inhibited the migration and invasion of breast cancer cells and suppressed the expressions of EMT, MMP-9, MMP-13, and other osteoclastic activators. HA inhibited EMT and MMP-9 by activating the ROS/JNK pathway as demonstrated by siJNK and SP600125 inhibition of JNK phosphorylation and NAC scavenging of ROS accumulation. Moreover, HA promoted bone formation and inhibited bone resorption in vitro. In conclusion, our findings suggest that HA may be an excellent candidate for treating breast cancer bone metastasis.
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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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2023
·
IF 5.7
Ding Wenbin,Zhou Qirong,Lu Yifeng,Wei Qiang,Tang Hao,Zhang Donghua,Liu Zhixiao,Wang Guangchao,Wu Dajiang
Stem cell-based therapy has drawn attention as an alternative option for promoting prosthetic osteointegration in osteoporosis by virtue of its unique characteristics. However, estrogen deficiency is the main mechanism of postmenopausal osteoporosis. Estrogen, as an effective antioxidant, deficienncy also results in the accumulation of reactive oxygen species (ROS) in the body, affecting the osteogenic differentiation of stem cells and the bone formation i osteoporosis. In this study, we prepared a ROS-scavenging hydrogel by crosslinking of epigallocatechin-3-gallate (EGCG), 3-acrylamido phenylboronic acid (APBA) and acrylamide. The engineered hydrogel can scavenge ROS efficiently, enabling it to be a cell carrier of bone marrow-derived mesenchymal stem cells (BMSCs) to protect delivered cells from ROS-mediated death and osteogenesis inhibition, favorably enhancing the tissue repair potential of stem cells. Further in vivo investigations seriously demonstrated that this ROS-scavenging hydrogel encapsulated with BMSCs can prominently promote osteointegration of 3D printed microporous titanium alloy prosthesis in osteoporosis, including scavenging accumulated ROS, inducing macrophages to polarize toward M2 phenotype, suppressing inflammatory cytokines expression, and improving osteogenesis related markers (e.g., ALP, Runx-2, COL-1, BSP, OCN, and OPN). This work provides a novel strategy for conquering the challenge of transplanted stem cells cannot fully function in the impaired microenvironment, and enhancing prosthetic osteointegration in osteoporosis.
研究领域:
生物材料
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组织工程
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再生医学
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骨科
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干细胞生物学
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2024
·
IF 9.4
Yunqing Tian,Yiming Ma,Yuxiang Kang,Shu Tian,Qingsi Li,Lei Zhang,Jing Yang
Hypothermic preservation (HP) is highly desired for the maintenance of the viability of living cell specimens, e.g. rare cells in whole-blood samples or therapeutic cells, in an unfrozen state. However, the extension of the viable preservation time is a challenge because of the multiple injuries suffered by hypothermically preserved cells. Here, based on a dynamic bond crosslinked zwitterionic hydrogel, we established a sensing preservation system that could monitor the levels of reactive oxygen species (ROS) via real-time electronic signals and intelligent control of antioxidant addition, to completely prevent an excess of ROS in the whole-cell specimen. Furthermore, the hydrogel-based system can counter the extracellular-matrix-loss-induced anoikis of living cells. Based on the design aimed at affording protection against two primary HP injuries (i.e. ROS overproduction and anoikis) to cells, this system extended the preservation time of cell specimens under refrigerated conditions to 24 days. After preservation, the use of a mild cell retrieval process guaranteed the activity of the preserved living cells. This work not only possesses the potential to facilitate intelligent cell-based clinical applications, but also paves the way for the preparation of living materials that can host programmed cells with long-term survival. Statement of significance An intelligent system based on a zwitterionic sensing hydrogel is established, which can afford ultra-long hypothermic cell-preservation times of up to 24 days. The system enables the real-time monitoring of ROS overproduction and intelligent antioxidant addition, because of the merging of the smart hydrogel with a computer intelligent detection and control system. Furthermore, the automatic addition of an antioxidant according to the ROS-signal changes produced by the ZBA hydrogel effectively prevented HP lesions, including ROS over-production and ECM loss, in the preserved living cells. Subsequently, the system could also be gently dissociated, to retrieve the preserved cells. This work provides a solution for the real-time monitoring and long-term HP of living specimens, which holds the promise of benefiting cell-based medicine and the development of genetically programmed cell-based living materials.
研究领域:
生物技术
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细胞生物学
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材料科学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
iScience
·
2023
·
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
·
纳米技术
·
骨科
·
炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Yang You,Yipu Liu,Chuchu Ma,Jianpei Xu,Laozhi Xie,Shiqiang Tong,Yinzhe Sun,Fenfen Ma,Yukun Huang,Junbin Liu,Wenze Xiao,Chengxiang Dai,Suke Li,Jigang Lei,Qiyong Mei,Xiaoling Gao,Jun Chen
Mesenchymal stem cells (MSCs) exhibited remarkable therapeutic potential in ischemic stroke due to their exceptional immunomodulatory ability and paracrine effect; they have also been regarded as excellent neuroprotectant delivery vehicles with inflammatory tropism. However, the presence of high levels of reactive oxygen species (ROS) and an oxidative stress environment at the lesion site inhibits cell survival and further therapeutic effects. Using bioorthogonal click chemistry, ROS-responsive luteolin-loaded micelles were tethered to the surface of MSCs. As MSCs migrated to the ischemic brain, the micelles would achieve ROS-responsive release of luteolin to protect MSCs from excessive oxidative damage while inhibiting neuroinflammation and scavenging ROS to ameliorate ischemic stroke. This study provided an effective and prospective therapeutic strategy for ischemic stroke and a framework for a stem cell-based therapeutic system to treat inflammatory cerebral diseases.
研究领域:
神经科学
·
干细胞治疗
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药学
·
炎症性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Theranostics
·
2024
·
IF 12.4
Hang Zhou,Zhongyuan He,Youde Cao,Lei Chu,Bing Liang,Kexiao Yu,Zhongliang Deng
Background: The repair of osteoporotic bone defects remains challenging due to excessive reactive oxygen species (ROS), persistent inflammation, and an imbalance between osteogenesis and osteoclastogenesis. Methods: Here, an injectable H 2 -releasing hydrogel (magnesium@polyethylene glycol-poly(lactic-co-glycolic acid), Mg@PEG-PLGA) was developed to remodel the challenging bone environment and accelerate the repair of osteoporotic bone defects. Results: This Mg@PEG-PLGA gel shows excellent injectability, shape adaptability, and phase-transition ability, can fill irregular bone defect areas via minimally invasive injection, and can transform into a porous scaffold in situ to provide mechanical support. With the appropriate release of H 2 and magnesium ions, the 2Mg@PEG-PLGA gel (loaded with 2 mg of Mg) displayed significant immunomodulatory effects through reducing intracellular ROS, guiding macrophage polarization toward the M2 phenotype, and inhibiting the IκB/NF-κB signaling pathway. Moreover, in vitro experiments showed that the 2Mg@PEG-PLGA gel inhibited osteoclastogenesis while promoting osteogenesis. Most notably, in animal experiments, the 2Mg@PEG-PLGA gel significantly promoted the repair of osteoporotic bone defects in vivo by scavenging ROS and inhibiting inflammation and osteoclastogenesis. Conclusions: Overall, our study provides critical insight into the design and development of H 2 -releasing magnesium-based hydrogels as potential implants for repairing osteoporotic bone defects.
研究领域:
生物医学工程
·
材料科学
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骨科
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再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2025
·Vol. 17
·期 10
·1263
·
IF 5.5
Jin Xue,Zifan Qiao,Shiyu Huang,Mubarak G. Bello,Lihua Chen
Background/Objectives:Ulcerative colitis (UC) involves chronic colon inflammation and oxidative stress. Treating UC is challenging due to systemic drug side effects and poor targeted delivery. Nanocarriers responsive to the UC microenvironment, particularly elevated reactive oxygen species (ROS), could overcome these limitations. This study developed an oral delivery system for ROS-triggered drug release and active targeting. Using ferulic acid (FER), a system was designed to enhance site-specific accumulation and therapeutic efficacy against colitis.Methods:A ROS-sensitive covalent organic framework (COF) was synthesized from γ-cyclodextrin and functionalized with folic acid (FA) to create a carrier (COF-FA) designed for potential active targeting. This carrier was loaded with FER to form FER@COF-FA. The system was characterized (SEM, FTIR, TGA), and its ROS scavenging and sustained drug release profiles were confirmed in vitro. Biocompatibility was evaluated in cell lines, and therapeutic efficacy was tested in a DSS-induced murine colitis model.Results:The synthesized FER@COF-FA demonstrated high drug loading, potent ROS-scavenging capability, and a sustained drug release profile. It showed excellent biocompatibility and, in the murine model, significantly outperformed free FER. Treatment alleviated disease severity, prevented colon shortening, restored healthy tissue histology, and rebalanced pro- and anti-inflammatory cytokines.Conclusions:The FER@COF-FA system represents a highly promising therapeutic strategy for UC. Its superior efficacy is attributed to a synergistic multi-mechanism approach, combining sustained release, ROS-responsive drug delivery, intrinsic antioxidant activity, and potential folate receptor-mediated targeting, which collectively enhance site-specific accumulation and therapeutic outcomes in the inflammatory colon microenvironment.
研究领域:
纳米医学
·
炎症性肠病
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药物递送系统
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生物材料
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氧化应激
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胃肠药理学
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转化医学
✓ 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）