Journal
BIOMATERIALS
Volume 31, Issue 33, Pages 8780-8788Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2010.07.086
Keywords
Chitosan; Small interfering RNA; Poly(gamma-glutamic acid); Transfection; Gene silencing
Funding
- National Science Council Taiwan, Republic of China [NSC 98-2120-M-007-007]
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Although advantageous for siRNA packing and protection, chitosan (CS)-based complexes may lead to difficulties in siRNA release once they arrive at the site of action, due to their electrostatic interactions. To assist the intracellular release of siRNA and thus enhance its effectiveness in gene silencing, we incorporated a negatively charged poly(gamma-glutamic acid) (gamma-PGA) into CS/siRNA complexes. The inclusion of gamma-PGA did not alter the complex-formation ability between CS and siRNA; additionally, their cellular uptake was significantly enhanced. The results obtained in our molecular dynamic simulations indicate that the binding between CS and siRNA remained stable in the cytosol environment. In contrast, the compact structure of the ternary CS/siRNA/gamma-PGA complexes was unpacked; such a structural unpackage may facilitate the intracellular release of siRNA. In the gene silencing study, we found that the inclusion of gamma-PGA into complexes could significantly expedite the onset of gene knockdown, enhance their inhibition efficiency and prolong the duration of gene silencing. These findings may be attributed to the fact that there were significantly more CS/siRNA/gamma-PGA complexes internalized into the cells in company with their more rapid intracellular unpackage and release of siRNA when compared with their binary counterparts in the absence of gamma-PGA. The aforementioned results suggest that CS/siRNA/gamma-PGA complexes can be an efficient vector for siRNA transfection. (C) 2010 Elsevier Ltd. All rights reserved.
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