title: Thermogelling polymer-platinum(IV) conjugates for long-term delivery of cisplatin.
abstract: In this study, we suggest a novel strategy of constituting an in situ-formed hydrogel composed of polymer-platinum(IV) conjugate to realize a long-term delivery of cisplatin. A unique conjugate was designed and synthesized by covalent linking of Pt(IV) complex to the hydrophobic end of two methoxyl poly(ethylene glycol)-b-poly(d,l-lactide) (mPEG-PLA) copolymer chains, resulting in the formation of Bi(mPEG-PLA)-Pt(IV). The conjugate could self-assemble into micelles in water, and its concentrated solution exhibited a thermoreversible sol-gel transition and formed a semisolid thermogel at body temperature. The incorporation of the cisplatin analogue Pt(IV) prodrug into the conjugate had a significant influence on its thermogelling properties and the conjugate thermogelation was attributed to the micellar aggregation. In vitro release experiments of Pt(IV)-conjugated thermogel showed that the platinum release lasted as long as two months. Furthermore, we demonstrated that the Pt(IV) prodrug was released mainly in the form of micelles and micellar aggregates from the gel depot. Compared with free cisplatin, the formation of conjugate micelles led to the enhanced in vitro cytotoxicity against cancer cells due to the effective accumulation into cells via endocytosis.
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University , Shanghai 200433, China.
authors.forename: Wenjia
authors.initials: W
authors.lastname: Shen
authors.forename: Jiabin
authors.initials: J
authors.lastname: Luan
authors.forename: Luping
authors.initials: L
authors.lastname: Cao
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.forename: Lin
authors.initials: L
authors.lastname: Yu
authors.forename: Jiandong
authors.initials: J
authors.lastname: Ding
mesh_terms: D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D020100:Hydrogels / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D010984:Platinum / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism
chemical_list: D004337:Drug Carriers; D020100:Hydrogels; D011108:Polymers; D010984:Platinum; D002945:Cisplatin