title: Improving aqueous solubility and antitumor effects by nanosized gambogic acid-mPEG₂₀₀₀ micelles.
abstract: The clinical application of gambogic acid, a natural component with promising antitumor activity, is limited due to its extremely poor aqueous solubility, short half-life in blood, and severe systemic toxicity. To solve these problems, an amphiphilic polymer-drug conjugate was prepared by attachment of low molecular weight (ie, 2 kDa) methoxy poly(ethylene glycol) methyl ether (mPEG) to gambogic acid (GA-mPEG₂₀₀₀) through an ester linkage and characterized by (1)H nuclear magnetic resonance. The GA-mPEG₂₀₀₀ conjugates self-assembled to form nanosized micelles, with mean diameters of less than 50 nm, and a very narrow particle size distribution. The properties of the GA-mPEG₂₀₀₀ micelles, including morphology, stability, molecular modeling, and drug release profile, were evaluated. MTT (3-(4,5-dimethylthiazo l-2-yl)-2,5 diphenyl tetrazolium bromide) tests demonstrated that the GA-mPEG₂₀₀₀ micelle formulation had obvious cytotoxicity to tumor cells and human umbilical vein endothelial cells. Further, GA-mPEG₂₀₀₀ micelles were effective in inhibiting tumor growth and prolonged survival in subcutaneous B16-F10 and C26 tumor models. Our findings suggest that GA-mPEG₂₀₀₀ micelles may have promising applications in tumor therapy.
authors.affiliation: Department of Pharmacy, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, People's Republic of China.
authors.forename: Lulu
authors.initials: L
authors.lastname: Cai
authors.affiliation: College of Materials and Chemistry and Chemical Engineering, Chengdu University of Technology, People's Republic of China.
authors.forename: Neng
authors.initials: N
authors.lastname: Qiu
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Mingli
authors.initials: M
authors.lastname: Xiang
authors.affiliation: Department of Pharmacy, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, People's Republic of China.
authors.forename: Rongsheng
authors.initials: R
authors.lastname: Tong
authors.affiliation: Department of Pharmacy, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, People's Republic of China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Pharmacy, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Pharmacy, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, People's Republic of China.
authors.forename: Jianyou
authors.initials: J
authors.lastname: Shi
authors.affiliation: Faculty of Pharmacy, University of Montreal, Montreal, QC, Canada.
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Jiaolin
authors.initials: J
authors.lastname: Wen
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry; D001834:Body Water / Q000737:chemistry*; D045744:Cell Line, Tumor; D004357:Drug Synergism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008823:Micelles; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D009374:Neoplasms, Experimental / Q000737:chemistry* / Q000188:drug therapy*; D011092:Polyethylene Glycols / Q000737:chemistry*; D012995:Solubility; D016896:Treatment Outcome; D044004:Xanthones / Q000008:administration & dosage* / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D008823:Micelles; D053769:Nanocapsules; D044004:Xanthones; D011092:Polyethylene Glycols; C052659:gambogic acid
keywords: antitumor; gambogic acid; micelle; poly(ethylene glycol)-drug conjugate; toxicity