title: Biological characterization of folate-decorated biodegradable polymer-platinum(II) complex micelles.
abstract: A biodegradable and amphiphilic copolymer, poly(ethylene glycol)-block-poly(l-lactide-co-2-methyl-2-carboxyl-propylene carbonate) (mPEG-b-P(LA-co-MCC)), which contains pendant carboxyl groups, was chosen as a drug carrier for the active anticancer part (diaminocyclohexane platinum, DACH-Pt) of oxaliplatin to form mPEG-b-P(LA-co-MCC/Pt) complex. A folic acid-conjugated copolymer, folic acid-poly(ethylene glycol)-block-poly(L-lactide) (FA-PEG-PLA), with similar chemical structure was chosen for targeting. Multifunctional micelles were successfully prepared by a coassembling method. In vitro evaluation was performed by using SKOV-3 and MCF-7 cancer cells. In vivo blood clearance of platinum was studied, and the results show that micelles exhibit longer blood circulation after iv injection. Pt biodistribution was studied by measuring its levels in plasma, organs, and tumors, especially in tumor cell DNA, by atomic absorption and inductively coupled plasma mass spectrometry. Antitumor activity was assessed in mice bearing H22 liver cancers, and the results showed that the micelles with FA moieties exhibited greater antitumor efficacy than those without FA or oxaliplatin. Therefore, these novel multifunctional platinum micelles have great potential in future clinical application.
authors.affiliation: State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, People's Republic of China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Xiuli
authors.initials: X
authors.lastname: Hu
authors.forename: Sai
authors.initials: S
authors.lastname: Wu
authors.forename: Haihua
authors.initials: H
authors.lastname: Xiao
authors.forename: Haidong
authors.initials: H
authors.lastname: Cai
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Xie
authors.forename: Yubin
authors.initials: Y
authors.lastname: Huang
authors.forename: Xiabin
authors.initials: X
authors.lastname: Jing
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005260:Female; D005492:Folic Acid / Q000737:chemistry*; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D013058:Mass Spectrometry; D051379:Mice; D008823:Micelles; D009944:Organoplatinum Compounds / Q000493:pharmacokinetics / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000473:pathology; D000077150:Oxaliplatin; D011108:Polymers / Q000737:chemistry*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D004337:Drug Carriers; D008823:Micelles; D009944:Organoplatinum Compounds; D011108:Polymers; D000077150:Oxaliplatin; D005492:Folic Acid