详细记录  
题名:Reducible poly(amido ethylenimine) directed to enhance RNA interference
作者:Ji Hoon Jeong, Lane V. Christensen, James W. Yockman, Zhiyuan Zhong, Johan F.J. Engbersen, Won Jong Kim, Jan Feijen and Sung Wan Kim
来源:Biomaterials[IF=4.698], Volume 28, Issue 10, April 2007, Pages 1912-1917
URL :http://dx.doi.org/10.1016/j.biomaterials.2006.12.019
日期:070415
摘要: Ji Hoon Jeonga, Lane V. Christensena, James W. Yockmana, Zhiyuan Zhongb, Johan F.J. Engbersenb, Won Jong Kima, Jan Feijenb and Sung Wan Kima, ,

aCCCD/Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA
bDepartment of Polymer Chemistry and Biomaterials, and Institute for Biomedical Technology (BMTI), Faculty of Science and Technology, University of Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands

Received 8 September 2006; accepted 4 December 2006. Available online 10 January 2007.

Summary

Designing synthetic macromolecular vehicles with high transfection efficiency and low cytotoxicity has been a major interest in the development of non-viral gene carriers. A reducible poly(amido ethylenimine) (SS-PAEI) synthesized by addition copolymerization of triethylenetetramine and cystamine bis-acrylamide (poly(TETA/CBA)) was used as a carrier for small interference RNA (siRNA). Poly(TETA/CBA) could efficiently condense siRNA to form stable complexes under physiological conditions and perform complete release of siRNA in a reductive environment. When formulated with VEGF-directed siRNA, poly(TETA/CBA) demonstrated significantly higher suppression of VEGF than linear-polyethylenimine (PEI) (L-PEI, 25 kDa) in human prostate cancer cells (PC-3). After 5 h of transfection, substantial dissociation and intracellular distribution of siRNA was observed in the poly(TETA/CBA) formulation, but not in the L-PEI formulation. The triggered release of siRNA by reductive degradation of poly(TETA/CBA) in the cytoplasm may affect the RNAi activity by increasing cytoplasmic availability of siRNA. These results suggest that the rational design of non-viral carriers should involve considerations for intracellular dissociation and trafficking of a nucleic acid drug to maximize its effect, in conjunction with formation of stable complexes under physiological conditions. 10.

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