PMID- 18088093 OWN - NLM STAT- MEDLINE DCOM- 20080331 LR - 20181201 IS - 1526-4602 (Electronic) IS - 1525-7797 (Linking) VI - 9 IP - 1 DP - 2008 Jan TI - An acid-labile block copolymer of PDMAEMA and PEG as potential carrier for intelligent gene delivery systems. PG - 109-15 AB - 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. FAU - Lin, Song AU - Lin S AD - 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. FAU - Du, Fusheng AU - Du F FAU - Wang, Yang AU - Wang Y FAU - Ji, Shouping AU - Ji S FAU - Liang, Dehai AU - Liang D FAU - Yu, Lei AU - Yu L FAU - Li, Zichen AU - Li Z LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20071219 PL - United States TA - Biomacromolecules JT - Biomacromolecules JID - 100892849 RN - 0 (Acids) RN - 0 (Drug Carriers) RN - 0 (Methacrylates) RN - 0 (Nylons) RN - 0 (poly(2-(dimethylamino)ethyl methacrylate)) RN - 3WJQ0SDW1A (Polyethylene Glycols) SB - IM MH - Acids/*chemistry MH - Drug Carriers MH - Electrophoresis, Agar Gel MH - Erythrocytes/drug effects MH - Hemolysis MH - Humans MH - Hydrogen-Ion Concentration MH - In Vitro Techniques MH - Methacrylates/*chemistry/pharmacology MH - Nylons/*chemistry/pharmacology MH - Particle Size MH - Polyethylene Glycols/*chemistry/pharmacology MH - *Transfection EDAT- 2007/12/20 09:00 MHDA- 2008/04/01 09:00 CRDT- 2007/12/20 09:00 PHST- 2007/12/20 09:00 [pubmed] PHST- 2008/04/01 09:00 [medline] PHST- 2007/12/20 09:00 [entrez] AID - 10.1021/bm7008747 [doi] PST - ppublish SO - Biomacromolecules. 2008 Jan;9(1):109-15. doi: 10.1021/bm7008747. Epub 2007 Dec 19.