PEG比率
雷公藤醇
细胞凋亡
化学
体内
卵巢癌
药物输送
癌症研究
癌细胞
体外
细胞生长
药理学
癌症
生物化学
医学
内科学
生物
生物技术
经济
有机化学
财务
作者
Ruisi Zhou,Yanting You,Zhiqiang Zha,Jiawen Chen,Yanchun Li,Xiaohu Chen,X. Chen,Xuefeng Jiang,Jinxiang Chen,Hiu Yee Kwan,Xiaoshan Zhao,Liping Huang,Yanyan Liu
标识
DOI:10.1016/j.biopha.2023.115573
摘要
Ovarian cancer (OC) stands as the second most prominent factor leading to cancer-related fatalities, characterized by a notably low five-year survival rate. The insidious onset of OC combined with its resistance to chemotherapy poses significant challenges in terms of treatment, emphasizing the utmost importance of developing innovative therapeutic agents. Despite its remarkable anti-tumor efficacy, celastrol (CEL) faces challenges regarding its clinical utilization in OC due to its restricted water solubility and notable side effects. In this study, celastrol (CEL) was encapsulated into Zeolitic imidazolate framework-8(ZIF-8) nanoparticle and grafted with biotin-conjugated polyethylene glycol (CEL@ZIF-8@PEG-BIO). Comprehensive comparisons of the physicochemical properties and anticancer activities of CEL and CEL@ZIF-8@PEG-BIO were conducted. Our findings revealed that CEL@ZIF-8@PEG-BIO exhibited favorable characteristics, including hydrodynamic diameters of 234.5 nm, excellent water solubility, high drug loading (31.60% ± 2.85), encapsulation efficiency (60.52% ± 2.79), and minimal side effects. Furthermore, CEL@ZIF-8@PEG-BIO can release chemicals in response to an acidic micro-environment, which is more likely a tumor micro-environment. In vitro, studies showed that CEL@ZIF-8@BIO inhibited cell proliferation, led to mitochondrial membrane potential (MMP) decline, and generated reactive oxygen species in OC cells. Both in vitro and in vivo experiments indicated that CEL@ZIF-8@PEG-BIO enhanced anti-tumor activity against OC via up-regulated apoptosis-promoting biomarkers and rendered cancer cell apoptosis via the P38/JNK MAPK signaling pathway. In conclusion, we have successfully developed a novel drug delivery system (CEL@ZIF-8@PEG-BIO), resulting in significant improvements in both water solubility and anti-tumor efficacy thereby providing valuable insights for future clinical drug development.
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