title: A cross-linked polymeric micellar delivery system for cisplatin(IV) complex.
abstract: A polymeric cisplatin(IV) prodrug in the form of cross-linked micelles (M(Pt(IV)) was prepared by first constructing MPEG-b-PCL-b-PLL micelles and then attaching a cisplatin(IV) complex with two axial succinic moieties to the lysine residues of the carrier polymer in aqueous medium. The micelles obtained were characterized by TEM, DLS, and zeta potential measurement. Their in vitro release experiments were carried out at pH 7.4 and 5.0 or in the presence of 5mM sodium ascorbate (NaAsc). Results showed that the micelles were sensitive to both acidic hydrolysis and mild reducing agents; in the presence of 5mM NaAsc, cisplatin(II) was directly released and the released cisplatin(II) could chelate with nucleobases; the micelles displayed comparable cytotoxicities to cisplatin; and the micelles were much more efficiently internalized by the cells than cisplatin(II) and cisplatin(IV) counterparts. Moreover, in vivo study showed accumulation of more Pt species in the tumor site and lower systematic toxicity compared to free cisplatin(II) and cisplatin(IV). This polymeric prodrug of cisplatin is expected to be used more for future study and applications.
authors.affiliation: Department of Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, People's Republic of China.
authors.forename: Haiqin
authors.initials: H
authors.lastname: Song
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Haihua
authors.initials: H
authors.lastname: Xiao
authors.forename: Haidong
authors.initials: H
authors.lastname: Cai
authors.forename: Wenjing
authors.initials: W
authors.lastname: Zhang
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
authors.forename: Tongjun
authors.initials: T
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D003432:Cross-Linking Reagents / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008819:Mice, Nude; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D011091:Polyesters / Q000737:chemistry*; D011107:Polylysine / Q000737:chemistry*; D011355:Prodrugs; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D008823:Micelles; D011091:Polyesters; D011355:Prodrugs; C572240:methoxy poly(ethylene glycol)-b-poly(epsilon-caprolactone)-b-poly(L-lysine); D011107:Polylysine; D002945:Cisplatin