title: A pH- and thermo-responsive poly(amino acid)-based drug delivery system.
abstract: A pH- and thermo-responsive poly(amino acid)-based amphiphilic copolymer was developed, functioning as a tumour targeting drug delivery system with good biocompatibility and biodegradability. To provide multi-stimuli sensitivity characteristics to the poly(amino acid)s, the polyaspartamide scaffold has been functionalized with N,N-diisopropylamide groups via aminolysis reaction of polysuccinimide. PEG chains have also been chemically grafted to the poly(amino acid) backbone through acid-labile hydrazone linkages, providing a removable shield for the poly(amino acid) based nanoparticles. Furthermore, doxorubicin was chemically linked to the copolymer chain via hydrazone bonds, acting as the hydrophobic moiety to drive the polymeric self-assembly. Free doxorubicin molecules could be encapsulated into the self-assembled nanoparticles via hydrophobic interactions and molecular π-π stacking. The results obtained show that the drug release can be triggered by the temperature with a significantly increased release being observed under acidic conditions. The cytotoxicity behaviour of the copolymers and drug-loaded nanoparticles was investigated in vitro at varying pH values and different temperatures. In doing so, superior characteristics concerning compatibility and anti-cancer activity could be observed.
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: Bingqiang
authors.initials: B
authors.lastname: Li
authors.affiliation: Key Laboratory of Functional Polymer Materials, Institute of Polymer Chemistry, Nankai University, Tianjin 300071, PR China.
authors.forename: Chu
authors.initials: C
authors.lastname: Gong
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: D000596:Amino Acids / Q000737:chemistry / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems; D006863:Hydrogen-Ion Concentration; D066244:Proton Magnetic Resonance Spectroscopy; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000596:Amino Acids
keywords: Drug delivery; Poly(amino acid); Stimuli-responsive; Thermo-responsive; pH-sensitive