title: pH-Triggered charge-reversal polypeptide nanoparticles for cisplatin delivery: preparation and in vitro evaluation.
abstract: A series of pH-responsive random copolymer poly(l-glutamic acid-co-l-lysine) [P(Glu-co-Lys)] were synthesized through the ring-opening polymerization (ROP) of γ-benzyl-l-glutamate N-carboxyanhydride (BLG-NCA) and 3-benzyloxycarbonyl-l-lysine N-carboxyanhydride (ZLys-NCA) and the subsequent deprotection. The chemical structure of the P(Glu-co-Lys)s was confirmed by NMR. Critical aggregation concentration and transmission electron microscopy measurements indicated that the P(Glu-co-Lys)s could self-assemble into aggregates in phosphate buffer. The surface charge of P(Glu-co-Lys) aggregates was greatly affected by the solution's pH and l-glutamic acid/l-lysine ratio because the carboxyl and amino groups present on the P(Glu-co-Lys) aggregates could be protonated or deprotonated to become charged. The pH value of the solution at which the surface charge of the P(Glu-co-Lys) aggregates reversed could be manipulated by the feed ratio of BLG-NCA and ZLys-NCA. In vitro methyl thiazolyl tetrazolium assays demonstrated that negatively charged P(Glu-co-Lys)s were nontoxic and biocompatible. Positive charged P(Glu-co-Lys)s showed some cytotoxicity to Hela cells. Cisplatin (CDDP) was used as a model anticancer drug to evaluate the charge-reversal drug delivery system. By the manipulation of CDDP loading content, the surface charge of the CDDP/P(Glu-co-Lys) nanoparticles could be reversed to positive from negative at tumor extracellular pH (pHe 6.5-7.2). An enhanced drug uptake and inhibition of cancer cell proliferation were observed for the tumoral pHe triggered charge-reversal CDDP/P(Glu-co-Lys) drug delivery system. These indicated that the CDDP/P(Glu-co-Lys) nanoparticles could be used as intelligent drug delivery systems for cancer therapy.
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Huang
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Tang
authors.forename: Xuefei
authors.initials: X
authors.lastname: Zhang
authors.forename: Haiyang
authors.initials: H
authors.lastname: Yu
authors.forename: Hai
authors.initials: H
authors.lastname: Sun
authors.forename: Xuan
authors.initials: X
authors.lastname: Pang
authors.forename: Xuesi
authors.initials: X
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002945:Cisplatin / Q000008:administration & dosage*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D053758:Nanoparticles; D010455:Peptides / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D010455:Peptides; D002945:Cisplatin