Poly(beta-amino ester) as a carrier for si/shRNA delivery in lung cancer cells.
Efficient delivery of small interfering RNA (siRNA) or small hairpin RNA (shRNA) is a critical concern in RNA interference (RNAi) studies. In the present study, we evaluated biodegradable poly(beta-amino ester) (PAE) carrier composed of low molecular weight polyethylenimine and poly(ethylene glycol) for si/shRNA delivery in lung cancer cells. PAE carrier successfully delivered EGFP (enhanced green fluorescence protein) siRNA (siGFP) and silenced EGFP expression. The silencing achieved with PAE carrier was found to be nearly 1.5 times superior and safer than standard PEI25K. Also, our PAE carrier exhibited superior Akt1 shRNA delivery (shAkt) and thereby silenced oncoprotein Akt1 efficiently. PAE-shAkt mediated Akt1 knock-down hindered cancer cell growth in Akt1 specific manner. Superior shAkt delivery and low cytotoxicity of PAE carrier promoted Akt1 knock-down specific apoptosis, while low delivery efficiency and high cytotoxicity of PEI25K carrier mainly exhibited undesirable necrosis. Moreover, basic cancer properties like cell proliferation, malignancy and metastasis were reduced more efficiently using PAE-shAkt system. These findings demonstrated the potential of PAE as an alternative to PEI25K in si/shRNA-based RNAi studies.
Jere
Dhananjay
D
Department of Agricultural Biotechnology, Seoul National University, Seoul 151-921, Republic of Korea.
Xu
Cheng-Xiong
CX
Arote
Rohidas
R
Yun
Cheol-Heui
CH
Cho
Myung-Haing
MH
Cho
Chong-Su
CS
D000280:Administration, Inhalation; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004337:Drug Carriers / Q000008:administration & dosage / Q000494:pharmacology*; D004952:Esters / Q000008:administration & dosage / Q000494:pharmacology*; D020868:Gene Silencing; D049452:Green Fluorescent Proteins / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009336:Necrosis; D011094:Polyethyleneimine / Q000494:pharmacology; D011108:Polymers / Q000008:administration & dosage / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000494:pharmacology*; D014162:Transfection
D004337:Drug Carriers; D004952:Esters; D011108:Polymers; D034741:RNA, Small Interfering; C485184:enhanced green fluorescent protein; C507253:poly(beta-amino ester); D049452:Green Fluorescent Proteins; D011094:Polyethyleneimine; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt