title: Facile preparation of a cationic poly(amino acid) vesicle for potential drug and gene co-delivery.
abstract: A novel pH-responsive poly(amino acid) grafted with oligocation was prepared through the combination of ring-opening polymerization (ROP) and subsequent atom transfer radical polymerization (ATRP). Firstly, poly(γ-2-chloroethyl-L-glutamate) (PCELG) with a pendent 2-chloroethyl group was synthesized through ROP of γ-2-chloroethyl-L-glutamate N-carboxyanhydride (CELG NCA) using n-hexylamine as the initiator. Then, PCELG was used to initiate the ARTP of 2-aminoethyl methacrylate hydrochloride (AMA), yielding poly(L-glutamate)-graft-oligo(2-aminoethyl methacrylate hydrochloride) (PLG-g-OAMA). The pK(a)  of PLG-g-OAMA was 7.3 established by the acid-base titration method. The amphiphilic poly(amino acid) could directly self-assemble into a vesicle in PBS. The vesicle was characterized by TEM and DLS. Hydrophilic DOX·HCl  was loaded into the hollow core of the vesicle. The in vitro release behavior of DOX·HCl  from the vesicle in PBS could be adjusted by the solution pH. In vitro cell experiments revealed that the vesicle could reduce the toxicity of the DOX·HCl. In addition, the preliminary gel retardation assay displayed that PLG-g-OAMA could efficiently bind DNA at a PLG-g-OAMA/DNA weight ratio of 0.3 or above, indicating its potential use as a gene carrier. More in-depth studies of the PLG-g-OAMA vesicle for drug and gene co-delivery in vitro and in vivo are in progress.
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: Jianxun
authors.initials: J
authors.lastname: Ding
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Xiao
authors.forename: Chaoliang
authors.initials: C
authors.lastname: He
authors.forename: Mingqiang
authors.initials: M
authors.lastname: Li
authors.forename: Di
authors.initials: D
authors.lastname: Li
authors.forename: Xiuli
authors.initials: X
authors.lastname: Zhuang
authors.forename: Xuesi
authors.initials: X
authors.lastname: Chen
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000494:pharmacology; D004247:DNA / Q000008:administration & dosage*; D003692:Delayed-Action Preparations / Q000138:chemical synthesis / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D008689:Methacrylates / Q000138:chemical synthesis / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy; D011099:Polyglutamic Acid / Q000138:chemical synthesis / Q000737:chemistry*; D058105:Polymerization
chemical_list: D000903:Antibiotics, Antineoplastic; D003692:Delayed-Action Preparations; D008689:Methacrylates; D011099:Polyglutamic Acid; C072703:2-aminoethylmethacrylate; D004317:Doxorubicin; D004247:DNA