Chitosan-graft-polyethylenimine for Akt1 siRNA delivery to lung cancer cells.

Abstract	Efficient delivery of small interfering RNA (siRNA) remains a challenging task in RNA interference (RNAi) studies. In this study, we used chitosan-graft-polyethylenimine (CHI-g-PEI) copolymer composed of chitosan and low molecular weight polyethylenimine (PEI) for the delivery of siRNA. The CHI-g-PEI carrier formed stable complexes with siRNA with compact spherical morphology. CHI-g-PEI delivered EGFP siRNA (siGFP) silenced EGFP expression nearly 2.5 folds higher than PEI25K at 50 pM siGFP concentration. Cell viability was found to be 2 folds high with CHI-g-PEI carrier than PEI25K. Also, our CHI-g-PEI carrier efficiently delivered Akt1 siRNA (siAkt) and thereby silenced onco-protein Akt1. Silencing of this crucial cell survival protein significantly reduced the lung cancer cell survival and proliferation. Additionally, Akt1 protein knock-down decreased A549 cell malignancy and metastasis. These findings suggest that the CHI-g-PEI carrier efficiently and safely delivered siRNA. Moreover, CHI-g-PEI mediated Akt1 siRNA delivery may emerge as a viable approach for lung cancer treatment.
Authors	Dhananjay Jere, Hu-Lin Jiang, You-Kyoung Kim, Rohidas Arote, Yun-Jaie Choi, Cheol-Heui Yun, Myung-Haing Cho, Chong-Su Cho
Journal	International journal of pharmaceutics (Int J Pharm) Vol. 378 Issue 1-2 Pg. 194-200 (Aug 13 2009) ISSN: 1873-3476 [Electronic] Netherlands
PMID	19501140 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Polymers RNA, Small Interfering enhanced green fluorescent protein Green Fluorescent Proteins Polyethyleneimine Chitosan AKT1 protein, human Proto-Oncogene Proteins c-akt
Topics	Cell Line, Tumor Cell Proliferation Cell Survival (genetics) Chitosan (chemistry) Gene Silencing Genetic Vectors (chemistry) Green Fluorescent Proteins (genetics) Humans Lung Neoplasms (genetics, metabolism) Polyethyleneimine (chemistry) Polymers (chemistry) Proto-Oncogene Proteins c-akt (genetics) RNA, Small Interfering (administration & dosage)

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