Ursodeoxycholic acid loaded dual-modified graphene oxide nanocomposite alleviates cholestatic liver injury through inhibiting hepatocyte apoptosis
作者全名：Zhou, Wanyi; Yang, Xinrui; Yin, Yaru; Chen, Si; Yang, Luxun; Li, Tao; Liu, Jing; Lu, Binghui; Yang, Zhangyou; Li, Rong; Zhang, Mingman
作者地址：[Zhou, Wanyi] Army Med Univ, Daping Hosp, Inst Surg Res, Army Med Ctr,Dept Urol, Chongqing 400042, Peoples R China; [Yang, Xinrui; Yin, Yaru; Yang, Luxun; Li, Tao; Liu, Jing; Lu, Binghui; Li, Rong] Army Med Univ, Coll Prevent Med, State Key Lab Trauma & Chem Poisoning, Mil Key Lab Nanomed, Chongqing 400038, Peoples R China; [Chen, Si; Zhang, Mingman] Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Dept Pediat Hepatobiliary Surg,Childrens Hosp, Minist Educ,Key Lab Child Dev & Disorders, Chongqing 400015, Peoples R China; [Yang, Zhangyou] Chongqing Med Univ, Coll Pharm, Chongqing Pharmacodynam Evaluat Engn Technol Res C, Chongqing Key Lab Pharmaceut Metab Res,Res Ctr, Chongqing 400016, Peoples R China
通信作者：Li, R (通讯作者)，Army Med Univ, Coll Prevent Med, State Key Lab Trauma & Chem Poisoning, Mil Key Lab Nanomed, Chongqing 400038, Peoples R China.; Zhang, MM (通讯作者)，Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Dept Pediat Hepatobiliary Surg,Childrens Hosp, Minist Educ,Key Lab Child Dev & Disorders, Chongqing 400015, Peoples R China.
来源：COLLOIDS AND SURFACES B-BIOINTERFACES
ESI学科分类：BIOLOGY & BIOCHEMISTRY
WOS号：WOS:001227161300001
JCR分区：Q1
影响因子：5.4
年份：2024
卷号：238
期号：
开始页：
结束页：
文献类型：Article
关键词：Ursodeoxycholic acid; Graphene oxide; Apoptosis; Autophagy; Cholestatic liver injury
摘要：Ursodeoxycholic acid (UDCA) is the preferred treatment for various types of cholestasis, however, its effectiveness is limited because of its insolubility in water. We used polyethylene glycol (PEG) and cationic polymer polyethylenimine (PEI) to double-modify graphite oxide (PPG) as a drug delivery system. UDCA was successfully loaded onto PPG through intermolecular interactions to form UDCA-PPG nanoparticles. UDCA-PPG nanoparticles not only improve the solubility and dispersibility of UDCA, but also have good biocompatibility and stability, which significantly improve the delivery rate of UDCA. The results indicated that UDCA-PPG significantly reduced ROS levels, promoted cell proliferation, protected mitochondrial membrane potential, reduced DNA damage and reduced apoptosis in the DCA-induced cell model. In a mouse cholestasis model established by bile duct ligation (BDL), UDCA-PPG improved liver necrosis, fibrosis, and mitochondrial damage and reduced serum ALT and AST levels, which were superior to those in the UDCA-treated group. UDCA-PPG reduced the expression of the apoptosis-related proteins, Caspase-3 and Bax, increased the expression of Bcl-2, and reduced the expression of the oxidative stress-related proteins, NQO and HO-1, as well as the autophagy-related proteins LC3, p62 and p-p62. Therefore, UDCA-PPG can enhance the therapeutic effect of UDCA in cholestasis, by significantly improving drug dispersibility and stability, extending circulation time in vivo, promoting absorption, decreasing ROS levels, enhancing autophagy flow and inhibiting apoptosis via the Bcl-2/Bax signaling pathway.
基金机构：National Natural Science Foundation of China [82173456]; Chongqing Natural Science Foundation [CSTC2021jcyj-msxm3803]; Sichuan Province Natural Science Foundation [2017SZ0004]; Technology Innovation and R & D Project of Chengdu Science and Technology Bureau [2021-YF05-01659-SN]
基金资助正文：This work was supported by the National Natural Science Foundation of China (No. 82173456), Chongqing Natural Science Foundation (CSTC2021jcyj-msxm3803), Sichuan Province Natural Science Foundation (2017SZ0004), Technology Innovation and R & D Project of Chengdu Science and Technology Bureau (2021-YF05-01659-SN) .
