title: pH-responsive zwitterionic polypeptide as a platform for anti-tumor drug delivery.
abstract: In this paper, a doxorubicin delivery system is reported based on a pH-responsive zwitterionic polypeptide derivative. To improve the anti-protein-fouling capacity, the poly(amino acid) was modified by grafting short-chain zwitterions via aminolysis reaction of polysuccinimide with l-lysine. As a result, both positively and negatively charged moieties were introduced onto the same side chain in a simultaneous fashion, providing a nano-scale homogenous mixture of balanced charges. The zwitterionic side chains serve as hydrophilic segments in the copolymer and feature excellent resistance to nonspecific protein adsorption. Doxorubicin was chemically grafted onto the poly(amino acid) moiety through acid-labile hydrazone linkages, providing removable hydrophobic segments and driving the polymer self-assembly. Free doxorubicin could be encapsulated into the self-assembled micelles via hydrophobic interactions and molecular π-π stacking. The results obtained show that the drug loaded nanoparticles exhibit excellent stabilities in protein solutions at pH=7.4 and significantly enhanced drug release characteristics under acidic conditions. The cytotoxicity characteristics of the zwitterionic copolymer and drug-loaded nanoparticles at different pH values were investigated in vitro and feature an excellent biocompatibility and anti-cancer activity, respectively.
authors.affiliation: Key Laboratory of Functional Polymer Materials, Institute of Polymer Chemistry, Nankai University, Tianjin 300071, PR China.
authors.forename: Na
authors.initials: N
authors.lastname: Liu
authors.affiliation: Key Laboratory of Functional Polymer Materials, Institute of Polymer Chemistry, Nankai University, Tianjin 300071, PR China.
authors.forename: Jiaming
authors.initials: J
authors.lastname: Han
authors.affiliation: Key Laboratory of Functional Polymer Materials, Institute of Polymer Chemistry, Nankai University, Tianjin 300071, PR China.
authors.forename: Xinchen
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Functional Polymer Materials, Institute of Polymer Chemistry, Nankai University, Tianjin 300071, PR China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yang
authors.affiliation: College of Pharmacy, Nankai University, Tianjin 300071, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: College of Pharmacy, Nankai University, Tianjin 300071, PR China.
authors.forename: Yanming
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of Functional Polymer Materials, Institute of Polymer Chemistry, Nankai University, Tianjin 300071, PR China. Electronic address: guolinwu@nankai.edu.cn.
authors.forename: Guolin
authors.initials: G
authors.lastname: Wu
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D011108:Polymers / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D011108:Polymers; D004317:Doxorubicin
keywords: Anti-protein adsorption; Drug delivery; Polypeptide; Stimuli-responsive; Zwitterionic polymer; pH-sensitive