Poly(beta-aminoester)s with pendant primary amines for efficient gene delivery.
Three hydrolytically degradable poly(beta-aminoester)s containing ester bonds in the main chain and primary amines in the side chain, synthesized by Michael polyaddition, were applied to deliver foreign DNA into cells in vitro. These linear polycations can condense DNA into small-sized particles with positive surface charge at high N/P ratios. Their high buffer capacity at pH 5-7 facilitated the escape of DNA from the endosome and resulted in efficient gene expression. Under the optimal conditions, poly(beta-aminoester)s with a pendant aminoethyl group showed higher transfection efficiencies than branched poly(ethylenimine) (PEI) 25KDa in 293T cells. The effect of side chain structure of the poly(beta-aminoester) on transfection efficiency has been investigated, which indicated that the poly(beta-aminoester) containing the pendant aminoethyl group was the most efficient carrier for both of 293T cells and COS-7 cells. The combination of hydrolytical degradation, high buffer capacity, relatively low cytotoxicity, and high transfection efficiency suggested that this kind of poly(beta-aminoester)s are novel promising nonviral gene carriers.
Liu
Min
M
Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan 430072, P. R. China.
Chen
Jun
J
Xue
Ya-Nan
YN
Liu
Wen-Ming
WM
Zhuo
Ren-Xi
RX
Huang
Shi-Wen
SW
D000588:Amines / Q000737:chemistry*; D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D004247:DNA / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D018014:Gene Transfer Techniques; D006801:Humans; D006863:Hydrogen-Ion Concentration; D010316:Particle Size; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013499:Surface Properties
D000588:Amines; D004337:Drug Carriers; D011108:Polymers; C507253:poly(beta-amino ester); D004247:DNA