MATERIALS & DESIGN
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2023
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IF 8.4
Daiwang Shi,Siyi Li,Wenhan Liu,Liang Song,Ran Xu
Lung cancer is a serious disease and the leading cause of cancer-related death. Metal-phenolic network nanoparticles have been proposed as a promising strategy for cancer therapy. In this work, eight-arm PEG succinimidyl glutarate, copper ions and doxorubicin (DOX) were integrated into one nanoparticle via hydrophobic interactions and coordination interactions to achieve chemotherapy (CT) and chemodynamic therapy (CDT). [email protected] accumulated in tumour tissue and released DOX and Cu 2+ into the tumour microenvironment. Cu 2+ reacted with GSH to form Cu + . Cu + continued to react with H 2 O 2 to form •OH. DOX killed lung cancer cells and activated NOX4, up-regulating the endogenous H 2 O 2 level and further enhancing the efficiency of CDT. In vitro and in vivo experiments demonstrated that [email protected] has superior biological safety and can inhibit the growth of lung cancer tumours via synergistic CT/CDT. This research offers a new strategy for the construction of metal-phenolic network nanoparticles for the synergistic treatment of lung cancer by CT/CDT.
研究领域:
肿瘤学
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纳米技术
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癌症治疗
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生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2019
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IF 3.361
Chunyan Li,Xiao Sun,Ang Li,Min Mo,Zhongxi Zhao
Pulmonary fibrosis (PF) is a disease characterized by diffusing alveolar inflammation and alveolar structural disorders that ultimately lead to pulmonary interstitial fibrosis. S-allylmercaptocysteine (SAMC) as a water-soluble organosulfur garlic derivative exhibits efficient anti-inflammatory and anti-oxidative activities. In this study, we attempted to explore the function of SAMC in inhibiting bleomycin (BLM)-induced pulmonary fibrosis in mice. 0.035 U/g of BLM was intraperitoneally injected into mice twice per week for 4 weeks to induce fibrosis. SAMC (25 and 50 mg/kg) and N-acetylcysteine (NAC, 600 mg/kg) were given to mice for 28 days. The results indicate that SAMC could significantly ameliorate the pathological structure, and decrease inflammatory cell infiltration and pro-inflammatory cytokines in bronchoalveolar lavage fluid (BALF) in BLM-induced pulmonary fibrosis mice. SAMC showed an anti-fibrosis effect by increasing anti-oxidants like HO-1, GSH and SOD as well as decreasing hydroxyproline (HYP) in BLM-induced mice. Mechanistic studies suggested that SAMC alleviated oxidative stress probably by impacting the Nox4/Nrf2 pathways, and played an anti-fibrosis role with decreasing the expression of α-SMA, collagen III, collagen I by suppressing the TGF-β1/Smad pathway. These findings indicate that SAMC may be partially responsible for the therapeutic effect on PF patients.
研究领域:
药理学
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肺科学
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免疫学
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病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Oxidative Medicine and Cellular Longevity
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2022
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IF 7.31
Dingyou Wang,Yuke Ji,Rui Wang,Ke Cheng,Liang Liu,Na Wu,Qing Tang,Xu Zheng,Junxia Li,Zhilong Zhu,Qinghua Wang,Xueyan Zhang,Runbo Li,Jinjin Pan,Zheng Sui,Yuhui Yuan
Hypoxic pulmonary hypertension (HPH) is a progressive cardiopulmonary system disease characterized by pulmonary vascular remodeling. Its occurrence and progression are closely related to oxidative stress. Lycopene, extracted from red vegetables and fruits, exhibits a particularly high antioxidant capacity that is beneficial for cardiovascular diseases. Nevertheless, the role and mechanism of lycopene in HPH remain unknown. Here, we found that lycopene reversed the elevated right ventricular systolic pressure (RVSP), right ventricular hypertrophy, and pulmonary vascular remodeling induced by hypoxia in rats. In vitro, lycopene caused lower proliferation and migration of PASMCs, with higher apoptosis. Consistent with the antiproliferative result of lycopene on hypoxic PASMCs, the hippo signaling pathway associated with cell growth was activated. Furthermore, lycopene reduced malondialdehyde (MDA) levels and enhanced superoxide dismutase (SOD) activity in the lungs and serum of rats under hypoxia conditions. The expression of NOX4 in the lungs was also significantly decreased. Hypoxic PASMCs subjected to lycopene showed decreased reactive oxygen species (ROS) production and NOX4 expression. Importantly, lycopene repressed HIF-1α expression both in the lungs and PASMCs in response to hypoxia in the absence of a significant change of HIF-1α mRNA. Compared with 2ME2 (a HIF-1α inhibitor) alone treatment, lycopene treatment did not significantly change PASMC proliferation, NOX4 expression, and ROS production after 2ME2 blocked HIF-1α, suggesting the inhibitory effect of lycopene on HIF-1α-NOX4-ROS axis and the targeted effect on HIF-1α. After CHX blocked protein synthesis, lycopene promoted the protein degradation of HIF-1α. MG-132, a proteasome inhibitor, notably reversed the decrease in HIF-1α protein level induced by lycopene in response to hypoxia. Therefore, lycopene suppressed hypoxia-induced oxidative stress through HIF-1α-NOX4-ROS axis, thereby alleviating HPH. Our findings will provide a new research direction for clinical HPH therapies.
研究领域:
心血管疾病
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药理学
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分子生物学
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细胞生物学
✓ 已验证
产品关联
DOI
高影响因子
ACS Nano
·
2023
·
IF 17.1
Ke Li,Kun Xu,Ye He,Yulu Yang,Meijun Tan,Yulan Mao,Yanan Zou,Qian Feng,Zhong Luo,Kaiyong Cai
The hypoxia microenvironment of solid tumors poses a technological bottleneck for ferroptosis and immunotherapy in clinical oncology. Nanoreactors based on special physiological signals in tumor cells are able to avoid various tumor tolerance mechanisms by alleviating the intracellular hypoxia environment. Herein we reported a nanoreactor Cu2–xSe that enabled the conversion of Cu elements between Cu+ and Cu2+ for the generation of O2 and the consumption of intracellular GSH content. Furthermore, to enhance the catalytic and ferroptosis-inducing activities of the nanoreactors, the ferroptosis agonist Erastin was loaded on the ZIF-8 coating on the surface of Cu2–xSe to up-regulate the expression of NOX4 protein, increase the intracellular H2O2 content, catalyze the Cu+ to produce O2 and activate ferroptosis. In addition, the nanoreactors were simultaneously surface functionalized with PEG polymer and folic acid molecules, which ensured the in vivo blood circulation and tumor-specific uptake. In vitro and in vivo experiments demonstrated that the functionalized self-supplying nanoreactors can amplify the ability to generate O2 and consume intracellular GSH via the interconversion of Cu elements Cu+ and Cu2+, and impair the GPX4/GSH pathway and HIF-1α protein expression. At the same time, by alleviating the intracellular hypoxia environment, the expression of miR301, a gene in the secreted exosomes was decreased, which ultimately affected the phenotype polarization of TAMs and increased the content of IFN γ secreted by CD8+ T cells, which further promoted the ferroptosis induced by Erastin-loaded nanoreactors. This combined therapeutic strategy of activating the tumor immune response and ferroptosis via self-supplying nanoreactors provides a potential strategy for clinical application.
研究领域:
肿瘤学
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纳米技术
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免疫治疗
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癌症生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
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2017
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IF 3.165
Xinyi Zhao,Rui Li,Ying Liu,Xuehong Zhang,Min Zhang,Zhi Zeng,Limin Wu,Xuelin Gao,Tian Lan,Yiqing Wang
Reactive oxygen species (ROS) play a key role in chronic liver injury and fibrosis. Polydatin, a glucoside of resveratrol , has been shown to possess anti-oxidative bioactivity. It has been demonstrated that resveratrol has many therapeutic effects on liver disorders including liver fibrosis. Recent study showed that polydatin prevented acute liver injury after carbon tetrachloride (CCl 4 ) induction. However, the protective effects of polydatin on chronic liver injury and fibrosis has not been understood. Thus, we aimed to determine the roles of polydatin in chronic liver injury and fibrosis. Mice were induced by CCl 4 for 6 weeks to develop chronic liver injury and fibrosis. Mice were treated with polydatin for 3 and 6 weeks, respectively. After 6 week injection of CCl 4 , the levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were markedly increased. The hepatic expression of α-SMA, collagen deposition and macrophage filtration were also increased. Furthermore, hepatic 4-HNE production and NOX4 expression were also increased in CCl 4 -induced mice. In contrast, polydatin ameliorated impaired liver function and histology. Moreover, polydatin attenuated liver fibrosis and inflammation in mice induced by CCl 4 . Additionally, polydatin suppressed hepatic 4-HNE production and NOX4 expression. In conclusion, polydatin ameliorate chronic liver injury and fibrosis through inhibition of oxidative stress and inflammation.
研究领域:
药理学
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肝病学
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毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2025
·
IF 16
Xu Zhang,Huan Yang,Ye He,Dan Zhang,Guifang Lu,Mudan Ren,Yi Lyu,Zhang Yuan,Shuixiang He
Excessive oxidative stress, dysregulated immune homeostasis, and disruption of the intestinal epithelial barrier are crucial features of inflammatory bowel disease (IBD). Traditional treatments focusing solely on inflammation resolution remain unsatisfactory. Herein, a yeast-inspired orally administered nanocomposite was developed. First, the MD@MPDA core was fabricated by integrating manganese dioxide (MnO2) nanozymes onto diallyl trisulfide (H2S prodrug)-loaded mesoporous polydopamine nanoparticles (MPDA). Then, yeast cell wall (YCW) was chosen to encapsulate MD@MPDA, namely, YMD@MPDA. The β-glucan embedded in the YCW shell not only protected the nanocomposite from the harsh gastrointestinal environment but also allowed the targeting enrichment in the inflamed colon. Furthermore, M1 macrophages triggered the intracellular GSH-responsive H2S release in the pathological microenvironment. MD@MPDA effectively alleviated inflammatory responses by MnO2-mediated ROS-scavenging and H2S-participated immunomodulation. The synergistic action contributed to macrophage mitochondrial function restoration and M2 polarization by suppressing NOX4 signaling and p38 MAPK pro-inflammatory signaling. In the mice model of dextran sulfate sodium (DSS)-induced IBD, the multipronged manner of scavenging oxidative stress, remodeling innate and adaptive immune homeostasis, and reshaping gut microbiota caused by YMD@MPDA effectively ameliorated inflammation and restored intestinal barrier functions. Overall, the YMD@MPDA nanocomposite provides a promising codelivery strategy of antioxidative nanozymes and gas prodrugs for the comprehensive management of IBD.
研究领域:
纳米医学
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胃肠病学
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免疫学
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药学
✓ 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）