Development of fluorinated polyplex nanoemulsions for improved small interfering RNA delivery and cancer therapy  

作　　者：Gang Chen Kaikai Wang Pengkai Wu Yixin Wang Zhanwei Zhou Lifang Yin Minjie Sun David Oupicky 

机构地区：[1]State Key Laboratory of Natural Medicines, Departmen t of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China [2]Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA

出　　处：《Nano Research》2018年第7期3746-3761,共16页纳米研究（英文版）

基　　金：This work was financially supported by the National Science and Technology Major Project （No. 2017YFA0205400）, the Changjiang Scholar program, the National Natural Science Foundation of China （Nos. 81373983 and 81573377）, China Postdoctoral Science Foundation （No. 2016M601923）, and Postgraduate Research ＆ Practice Innovation Program of Jiangsu Province （No. KYCX17_0671）.

摘　　要：We report the development of a small interfering RNA （siRNA） delivery vector based on cationic perfluorocarbon nanoemulsions. We have prepared perfluorodecalin （PFD） emulsions with a positive surface charge provided by a fluorinated poly（ethylenimine） （F-PEI）. The fluorinated emulsion （F-PEI@PFD） reduced cytotoxicity of F-PEI and demonstrated effective binding with siRNAs to form nanosized emulsion polyplexes. The prepared emulsion polyplexes enhanced cellular uptake and improved endosomal escape of the siRNA. In addition to increased reporter gene silencing in multiple cancer cell lines, when compared with control F-PEI and PEI polyplexes, the siR_NA emulsion polyplexes showed an excellent resistance to serum deactivation and maintained high activity, even in high-serum conditions. The F-PEI@PFD emulsion polyplexes carrying an siRNA to silence the expression of Bcl2 gene induced apoptosis and inhibited tumor growth in a melanoma mouse model in vivo and showed potential for in vivo ultrasound imaging. This study demonstrates the potential of F-PEI@PFD emulsions as a multifunctional theranostic nanoplatform for safe siRNA delivery, with integrated ultrasound imaging functionality.We report the development of a small interfering RNA （siRNA） delivery vector based on cationic perfluorocarbon nanoemulsions. We have prepared perfluorodecalin （PFD） emulsions with a positive surface charge provided by a fluorinated poly（ethylenimine） （F-PEI）. The fluorinated emulsion （F-PEI@PFD） reduced cytotoxicity of F-PEI and demonstrated effective binding with siRNAs to form nanosized emulsion polyplexes. The prepared emulsion polyplexes enhanced cellular uptake and improved endosomal escape of the siRNA. In addition to increased reporter gene silencing in multiple cancer cell lines, when compared with control F-PEI and PEI polyplexes, the siR_NA emulsion polyplexes showed an excellent resistance to serum deactivation and maintained high activity, even in high-serum conditions. The F-PEI@PFD emulsion polyplexes carrying an siRNA to silence the expression of Bcl2 gene induced apoptosis and inhibited tumor growth in a melanoma mouse model in vivo and showed potential for in vivo ultrasound imaging. This study demonstrates the potential of F-PEI@PFD emulsions as a multifunctional theranostic nanoplatform for safe siRNA delivery, with integrated ultrasound imaging functionality.

关 键 词：POLYPLEXES fluorous interactions small interfering RNA（siRNA） delivery tumor deliver perfluorocarbon emulsion 

分 类 号：Q959.8[生物学—动物学] TQ174.759[化学工程—陶瓷工业]