TY - JOUR
T1 - Water soluble poly(histamine acrylamide) with superior buffer capacity mediates efficient and nontoxic in vitro gene transfection
AU - Luo, Sibin
AU - Cheng, Ru
AU - Meng, Fenghua
AU - Park, Tae Gwan
AU - Zhong, Zhiyuan
PY - 2011/8/1
Y1 - 2011/8/1
N2 - Water-soluble cationic polymers, poly(histamine acrylamide)s (PHAs), with superior buffer capacity at the endosomal pH range were designed, prepared, and investigated for non-viral gene transfection. PHAs were obtained with molecular weights ranging from 9.2 to 28.7 kDa through controlled radical polymerization of histamine acrylamide (HA). Acid-base titration results displayed that all PHA polymers had a remarkably high buffer capacity of about 70% at pH 5.1-7.2. 12.7-28.7 kDa PHAs were able to effectively condense DNA into nano-sized (<220 nm) polyplexes with moderate positive surface charges (+13-+19 mV) at N/P ratios ≥10/1. CCK assays indicated that polyplexes of 12.7 and 17.5 kDa PHAs were non-toxic to COS-7 cells up to a tested N/P ratio of 20/1. Interestingly, the in vitro transfection using pCMV-Luc and pEGFP-C1 plasmid DNA as reporter genes showed that polyplexes of 12.7 kDa PHA formed at an N/P ratio of 20/1 mediated efficient transfection in COS-7 cells under 10% serum conditions, with transfection efficiencies comparable to that of 25 kDa polyethylenimine control. Their versatile design of structures, controlled synthesis, low cytotoxicity, and high transfection activity render PHA-based cationic polymers particularly interesting for the development of safe and efficient non-viral gene delivery systems.
AB - Water-soluble cationic polymers, poly(histamine acrylamide)s (PHAs), with superior buffer capacity at the endosomal pH range were designed, prepared, and investigated for non-viral gene transfection. PHAs were obtained with molecular weights ranging from 9.2 to 28.7 kDa through controlled radical polymerization of histamine acrylamide (HA). Acid-base titration results displayed that all PHA polymers had a remarkably high buffer capacity of about 70% at pH 5.1-7.2. 12.7-28.7 kDa PHAs were able to effectively condense DNA into nano-sized (<220 nm) polyplexes with moderate positive surface charges (+13-+19 mV) at N/P ratios ≥10/1. CCK assays indicated that polyplexes of 12.7 and 17.5 kDa PHAs were non-toxic to COS-7 cells up to a tested N/P ratio of 20/1. Interestingly, the in vitro transfection using pCMV-Luc and pEGFP-C1 plasmid DNA as reporter genes showed that polyplexes of 12.7 kDa PHA formed at an N/P ratio of 20/1 mediated efficient transfection in COS-7 cells under 10% serum conditions, with transfection efficiencies comparable to that of 25 kDa polyethylenimine control. Their versatile design of structures, controlled synthesis, low cytotoxicity, and high transfection activity render PHA-based cationic polymers particularly interesting for the development of safe and efficient non-viral gene delivery systems.
KW - biological applications of polymers
KW - gene delivery
KW - imidazole
KW - plasmid DNA
KW - proton sponge effect
KW - radical polymerization
KW - water soluble polymers
UR - http://www.scopus.com/inward/record.url?scp=79959721610&partnerID=8YFLogxK
U2 - 10.1002/pola.24773
DO - 10.1002/pola.24773
M3 - Article
AN - SCOPUS:79959721610
SN - 0887-624X
VL - 49
SP - 3366
EP - 3373
JO - Journal of Polymer Science, Part A: Polymer Chemistry
JF - Journal of Polymer Science, Part A: Polymer Chemistry
IS - 15
ER -