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Efficient Gene Delivery with Osmotically Active and Hyperbranched Poly(ester amine)s

Cited 40 time in Web of Science Cited 43 time in Scopus
Authors
Arote, Rohidas B.; Lee, Eun-Sun; Jiang, Hu-Lin; Kim, You-Kyoung; Choi, Yun-Jaie; Cho, Myung-Haing; Cho, Chong-Su
Issue Date
2009-12
Citation
Bioconjugate Chemistry, Vol.20 No.12, pp.2231-2241
Abstract
Degradable and hyperbranched poly (ester amine)s (PEAs) were successfully synthesized by Michael addition reaction between hydrophilic glycerol triacrylate (GTA) and low-molecular-weight polyethylenimine (LMW-PEI) and evaluated as nonviral gene carriers. PEAs effectively condensed DNA with particle sizes below 200 nm and suitable surface charges (15-45 mV), suitable for intracellular delivery. PEAs degraded in a controlled fashion showing half-lives of more than 12 days and were essentially nontoxic in three different cell lines. Elevated transfection levels by luciferase assay revealed the superiority of PEAs over PEI 25K and Lipofectamine. PEAs synthesized using 1:4 mol ratio of GTA to PEI [GTA/PEI-1.2(1:4)] showed highest transfection efficiency in HepG2 cells. PEAs showed significant gene expression in vitro as well as in vivo through aerosol administration. Reduction in packed cell volume (PCV) of cells when treated with polyplexes supported the hyperosmotic effect of PEAs. Effect of bafilomycin A1 on transfection efficiency of PEAs on 293T cells indicated its endosomal buffering capacity. High transfection efficiency wits attributed to the synergism from hyperosmotic glycerol backbone in the PEAs and endosomal buffering capacity of PEI amine groups. Therefore, this convergence of osmotically active biodegradable PEAs suggests their potential as it sale and efficient gene delivery vector.
ISSN
1043-1802
URI
https://hdl.handle.net/10371/172328
DOI
https://doi.org/10.1021/bc900184k
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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