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pubmed-article:21071079pubmed:abstractTextTo improve transfection efficiency and reduce the cytotoxicity of polymeric gene vectors, reducible polycations (RPC) were synthesized from low molecular weight (MW) branched polyethyleneimine (bPEI) via thiolation and oxidation. RPC (RPC-bPEI(0.8 kDa)) possessed MW of 5 kDa-80 kDa, and 50%-70% of the original proton buffering capacity of bPEI(0.8 kDa) was preserved in the final product. The cytotoxicity of RPC-bPEI(0.8 kDa) was 8-19 times less than that of the gold standard of polymeric transfection reagents, bPEI(25 kDa). Although bPEI(0.8 kDa) exhibited poor gene condensing capacities (?2 ?m at a weight ratio (WR) of 40), RPC-bPEI(0.8 kDa) effectively condensed plasmid DNA (pDNA) at a WR of 2. Moreover, RPC-bPEI(0.8 kDa)/pDNA (WR ?2) formed 100-200 nm-sized particles with positively charged surfaces (20-35 mV). In addition, the results of the present study indicated that thiol/polyanions triggered the release of pDNA from RPC-bPEI(0.8 kDa)/pDNA via the fragmentation of RPC-bPEI(0.8 kDa) and ion-exchange. With negligible polyplex-mediated cytotoxicity, the transfection efficiencies of RPC-bPEI(0.8 kDa)/pDNA were approximately 1200-1500-fold greater than that of bPEI(0.8 kDa)/pDNA and were equivalent or superior (?7-fold) to that of bPEI(25 kDa)/pDNA. Interestingly, the distribution of high MW RPC-bPEI(0.8 kDa)/pDNA in the nucleus of the cell was higher than that of low MW RPC-bPEI(0.8 kDa)/pDNA. Thus, the results of the present study suggest that RPC-bPEI(0.8 kDa) has the potential to effectively deliver genetic materials with lower levels of toxicity.lld:pubmed
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pubmed-article:21071079pubmed:authorpubmed-author:BaeYou HanYHlld:pubmed
pubmed-article:21071079pubmed:authorpubmed-author:KangHo-JungHJlld:pubmed
pubmed-article:21071079pubmed:authorpubmed-author:KangHan...lld:pubmed
pubmed-article:21071079pubmed:copyrightInfoCopyright © 2010 Elsevier Ltd. All rights reserved.lld:pubmed
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pubmed-article:21071079pubmed:volume32lld:pubmed
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pubmed-article:21071079pubmed:pagination1193-203lld:pubmed
pubmed-article:21071079pubmed:dateRevised2011-3-11lld:pubmed
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pubmed-article:21071079pubmed:articleTitleA reducible polycationic gene vector derived from thiolated low molecular weight branched polyethyleneimine linked by 2-iminothiolane.lld:pubmed
pubmed-article:21071079pubmed:affiliationDepartment of Pharmaceutics and Pharmaceutical Chemistry, The University of Utah, 421 Wakara way, Suite 318, Salt Lake City, UT 84108, USA.lld:pubmed
pubmed-article:21071079pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:21071079pubmed:publicationTypeResearch Support, N.I.H., Extramurallld:pubmed