title: A complex of cyclohexane-1,2-diaminoplatinum with an amphiphilic biodegradable polymer with pendant carboxyl groups.
abstract: A biodegradable and amphiphilic copolymer, MPEG-b-P(LA-co-MCC), which contains pendant carboxyl groups, was chosen as a drug carrier for the active anticancer part (DACH-Pt) of oxaliplatin to form an MPEG-b-P(LA-co-MCC/Pt) complex. It was able to self-assemble into micelles with a mean diameter of 30-40 nm, and a surface potential near -10 mV. The typical platinum content was 10 wt.%. The micelles showed acid-responsive drug release kinetics, which is beneficial for drug release in the intracellular environment. The Pt(II) species were released mainly in the form of DACH-Pt-Cl(2) in 150 mM NaCl solution and DACH-Pt(2+)-(H(2)O)(2) in pure water according to the results obtained by high-performance liquid chromatography coupled with inductively coupled plasma mass spectrometry and X-ray photoelectron spectroscopy. In vitro evaluation showed that the micelles displayed the same or higher cytotoxicities against SKOV-3, HeLa, and EC-109 cancer cells compared with oxaliplatin. The enhanced cytotoxicity against SKOV-3 cells is attributed to effective internalization of the micelles by the cells via endocytosis and the sensitivity of SKOV-3 cells to platinum drugs. This novel biodegradable and amphiphilic copolymer-based platinum drug will have great potential application in clinical use.
authors.affiliation: State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, People's Republic of China.
authors.forename: Haihua
authors.initials: H
authors.lastname: Xiao
authors.forename: Dongfang
authors.initials: D
authors.lastname: Zhou
authors.forename: Shi
authors.initials: S
authors.lastname: Liu
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Zheng
authors.forename: Yubin
authors.initials: Y
authors.lastname: Huang
authors.forename: Xiabin
authors.initials: X
authors.lastname: Jing
mesh_terms: D020341:Absorbable Implants; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage* / Q000737:chemistry; D004343:Drug Implants / Q000008:administration & dosage* / Q000138:chemical synthesis*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008422:Materials Testing; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D011108:Polymers / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D004343:Drug Implants; D011108:Polymers; D002945:Cisplatin