Aerosol delivery of folate-decorated hyperbranched polyspermine complexes to suppress lung tumorigenesis via Akt signaling pathway

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• 作者：Cheng-Qiong Luo^a ; ¹ ; Yoonjeong Jang^d ; ¹ ; Lei Xing^a ; Peng-Fei Cui^a ; Jian-Bin Qiao^a ; Ah Young Lee^d ; Hyeon-Jeong Kim^d ; Myung-Haing Cho^d ; ^{mchotox@snu.ac.kr" class="auth_mail" title="E-mail the corresponding author} ; Hu-Lin Jiang^a ; ^b ; ^c ; ^{jianghulin3@163.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：shAkt1 ; Aerosol delivery ; Lung cancer ; Biocompatibility ; Cancer cell targeting ; Gene therapy
• 刊名：International Journal of Pharmaceutics
• 出版年：2016
• 出版时间：20 November 2016
• 年：2016
• 卷：513
• 期：1-2
• 页码：591-601
• 全文大小：3666 K

文摘

Lung cancer has been a leading cause of cancer mortality worldwide and aerosol-mediated gene therapy endows numerous advantages compared to other traditional modalities. Here, we reported a folic acid (FA)-modified hyperbranched polyspermine (HPSPE) with prominent biocompatibility for lung cancer cell targeted gene therapy. FA was decorated to the HPSPE via an amidation reaction and the physicochemical properties of nanoplexes formed with DNA were characterized. Gel electrophoresis study elucidated that the designed polymer was capable to condense DNA and protect it from degradation by DNase I. Cell viability and transfection efficiency assay in vitro and in vivo indicated its increased transfection performance with lower toxicity. Furthermore, reduced tumor numbers and down-regulation of Akt1 protein after aerosol treatment containing FA-HPSPE/shAkt1 complexes proved its therapeutic potential for lung cancer suppression. Results obtained in this study suggested that FA-HPSPE with highly biocompatibility and targeting capability while forming complexes with shAkt1 and administrated through noninvasive aerosol could be prospective for inhibiting lung tumorigenesis.