title: Improving the anti-ovarian cancer activity of docetaxel with biodegradable self-assembly micelles through various evaluations.
abstract: Docetaxel (DOC) produces anti-tumor effects by inducing apoptosis and inhibiting cell growth. However, its clinical application is limited by its hydrophobicity and low biocompatibility. Therefore, improving DOC's water solubility, biocompatibility, and anti-tumor effects are important goals that will improve its clinical utility. In this work, DOC and methoxy poly(ethylene glycol) (MPEG)/polycaprolactone (PCL) (MPEG-PCL) showed good compatibility through computer simulations. We prepared DOC-loaded polymeric micelles (DOC/MPEG-PCL micelles) with drug loading of 6.82% and encapsulation efficiency of 98.36%; these were monodispersed and approximately 30 nm in diameter, and released DOC over an extended period in vitro and in vivo. In addition, DOC/MPEG-PCL micelles inhibited cell growth and induced apoptosis more effectively than free DOC in vitro. Furthermore, DOC/MPEG-PCL micelles inhibited ovarian tumor growth more significantly than free DOC. Immunohistochemical analysis indicated that DOC/MPEG-PCL micelles improved DOC's anti-tumor effect by enhancing tumor cell apoptosis and suppressing tumor cell proliferation. Moreover, in bio-imaging analysis, DOC/MPEG-PCL micelles showed a higher concentration and a longer retention time in ovarian tumor tissue than did free DOC, indicating that the DOC/MPEG-PCL micelles delivered more anti-tumor drug to the tumor. Our data suggest that DOC/MPEG-PCL micelles have the potential to be applied clinically in ovarian cancer therapy.
authors.affiliation: Department of Neurosurgery, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, and West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, PR China; Institute of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, PR China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Neurosurgery, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, and West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, PR China.
authors.forename: Shimin
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, and West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, PR China.
authors.forename: BiLan
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, and West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, PR China.
authors.forename: Senyi
authors.initials: S
authors.lastname: Deng
authors.affiliation: Department of Neurosurgery, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, and West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, PR China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pharmacology and Pharmaceutical Sciences, School of Medicine, Tsinghua University, Beijing, China.
authors.forename: XiaoNing
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, and West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, PR China.
authors.forename: LinLi
authors.initials: L
authors.lastname: Luo
authors.affiliation: Department of Neurosurgery, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, and West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, PR China.
authors.forename: RangRang
authors.initials: R
authors.lastname: Fan
authors.affiliation: Department of Neurosurgery, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, and West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, PR China. Electronic address: xiangmingli2018@163.com.
authors.forename: MingLi
authors.initials: M
authors.lastname: Xiang
authors.affiliation: Department of Neurosurgery, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, and West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, PR China; Institute of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: You
authors.affiliation: Department of Neurosurgery, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, and West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, PR China.
authors.forename: YuQuan
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Neurosurgery, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, and West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, PR China.
authors.forename: ZhiYong
authors.initials: Z
authors.lastname: Qian
authors.affiliation: Department of Neurosurgery, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, and West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, PR China. Electronic address: guogang@scu.edu.cn.
authors.forename: Gang
authors.initials: G
authors.lastname: Guo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017209:Apoptosis; D002455:Cell Division; D045744:Cell Line, Tumor; D003198:Computer Simulation; D000077143:Docetaxel; D004337:Drug Carriers; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D043823:Taxoids / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015027:Zebrafish
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D043823:Taxoids; D000077143:Docetaxel
keywords: Cell apoptosis; Cell growth; Docetaxel; MPEG-PCL; Ovarian cancer; Self-assembly