title: Polymeric nanoassemblies entrapping curcumin overcome multidrug resistance in ovarian cancer.
abstract: The increasing emergence of multidrug-resistant (MDR) cells presents a challenge to effective cancer therapy. Curcumin (CUR) has multifunctional anticancer properties, but its clinical use has been limited by poor solubility. We developed biodegradable polymeric micelles entrapping CUR in order to improve its antitumor activity and to explore whether it could treat MDR cells. This delivery system produced small micelles with a high encapsulation efficiency, good stability, and slow release of CUR. CUR micelles showed cytotoxic effects in wild-type drug-sensitive A2780s and in paclitaxel-resistant A2780t ovarian adenocarcinoma cells. The concentration of free CUR that reduced cell viability by 50% (IC50) was 1.5 fold and 1.2 fold higher than that of CUR micelles in A2780s and A2780t cells, respectively. Cellular uptake studies indicated that delivery by micelles improved CUR uptake into both cell lines. Cell cycle analysis suggested that CUR micelles induced apoptosis and enhanced G2/M arrest. Overall, CUR micelles may provide a novel strategy to improve the clinical management of MDR ovarian cancer.
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Qiheng
authors.initials: Q
authors.lastname: Gou
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Chunting
authors.initials: C
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Qinjie
authors.initials: Q
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Lu
authors.initials: L
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Medical Oncology, Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, PR China. Electronic address: leepingmd68@163.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China. Electronic address: chygong14@163.com.
authors.forename: Changyang
authors.initials: C
authors.lastname: Gong
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D008823:Micelles; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010316:Particle Size; D013499:Surface Properties
chemical_list: D000970:Antineoplastic Agents; D008823:Micelles; D003474:Curcumin
keywords: Biodegradable; Curcumin; MPEG-PCL copolymer; Micelles; Multidrug resistant; Ovarian cancer