Chitosan-graft-polyethylenimine for Akt1 siRNA delivery to lung cancer cells.
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.
Jere
Dhananjay
D
Department of Agricultural Biotechnology, Seoul National University, Seoul 151-921, Republic of Korea.
Jiang
Hu-Lin
HL
Kim
You-Kyoung
YK
Arote
Rohidas
R
Choi
Yun-Jaie
YJ
Yun
Cheol-Heui
CH
Cho
Myung-Haing
MH
Cho
Chong-Su
CS
D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D048271:Chitosan / Q000737:chemistry*; D020868:Gene Silencing; D005822:Genetic Vectors / Q000737:chemistry; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism; D011094:Polyethyleneimine / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D034741:RNA, Small Interfering / Q000008:administration & dosage*
D011108:Polymers; D034741:RNA, Small Interfering; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D011094:Polyethyleneimine; D048271:Chitosan; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt