title: An acid-labile block copolymer of PDMAEMA and PEG as potential carrier for intelligent gene delivery systems.
abstract: Intelligent gene delivery systems based on physiologically triggered reversible shielding technology have evinced enormous interest due to their potential in vivo applications. In the present work, an acid-labile block copolymer consisting of poly(ethylene glycol) and poly(2-(dimethylamino)ethyl methacrylate) segments connected through a cyclic ortho ester linkage (PEG- a-PDMAEMA) was synthesized by atom transfer radical polymerization of DMAEMA using a PEG macroinitiator with an acid-cleavable end group. PEG- a-PDMAEMA condensed with plasmid DNA formed polyplex nanoparticles with an acid-triggered reversible PEG shield. The pH-dependent shielding/deshielding effect of PEG chains on the polyplex particles were evaluated by zeta potential and size measurements. At pH 7.4, polyplexes generated from PEG- a-PDMAEMA exhibited smaller particle size, lower surface charge, reduced interaction with erythrocytes, and less cytotoxicity compared to PDMAEMA-derived polyplexes. At pH 5.0, zeta potential of polyplexes formed from PEG- a-PDMAEMA increased, leveled up after 2 h of incubation and gradual aggregation occurred in the presence of bovine serum albumin (BSA). In contrast, the stably shielded polyplexes formed by DNA and an acid-stable block copolymer, PEG- b-PDMAEMA, did not change in size and zeta potential in 6 h. In vitro transfection efficiency of the acid-labile copolymer greatly increased after 6 h incubation at pH 5.0, approaching the same level of PDMAEMA, whereas there was only slight increase in efficiency for the stable copolymer, PEG- b-PDMAEMA.
authors: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Polymer Chemistry and Physics of Ministry of Education, College of Chemistry & Molecular Engineering, Peking University, Beijing 100871, PR China.
authors: Song
authors: S
authors: Lin
authors: Fusheng
authors: F
authors: Du
authors: Yang
authors: Y
authors: Wang
authors: Shouping
authors: S
authors: Ji
authors: Dehai
authors: D
authors: Liang
authors: Lei
authors: L
authors: Yu
authors: Zichen
authors: Z
authors: Li
mesh_terms: D000143:Acids / Q000737:chemistry*; D004337:Drug Carriers; D004587:Electrophoresis, Agar Gel; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008689:Methacrylates / Q000737:chemistry* / Q000494:pharmacology; D009757:Nylons / Q000737:chemistry* / Q000494:pharmacology; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000494:pharmacology; D014162:Transfection
chemical_list: D000143:Acids; D004337:Drug Carriers; D008689:Methacrylates; D009757:Nylons; C407037:poly(2-(dimethylamino)ethyl methacrylate); D011092:Polyethylene Glycols