Folate-conjugated polyspermine for lung cancer-targeted gene therapy.

Mei Zhang; You-kyoung Kim; Pengfei Cui; Jialiang Zhang; Jianbin Qiao; Yujing HE; Jinyuan Lyu; Chengqiong Luo; Lei Xing; Hulin Jiang

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Folate-conjugated polyspermine for lung cancer-targeted gene therapy.

Author: Mei ZHANG ¹ ; You-Kyoung KIM ¹ ; Pengfei CUI ¹ ; Jialiang ZHANG ¹ ; Jianbin QIAO ¹ ; Yujing HE ¹ ; Jinyuan LYU ¹ ; Chengqiong LUO ¹ ; Lei XING ¹ ; Hulin JIANG ¹
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1. State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, China.
Publication Type:Journal Article
Keywords: Biocompatibility; Folate receptor; Folic acid; Gene therapy; Lung cancer; Non-viral gene vector; Polyspermine; Targeted gene delivery
From: Acta Pharmaceutica Sinica B 2016;6(4):336-343
CountryChina
Language:English
Abstract: Biodegradable polyamines have long been studied as potential recombinant viral gene vectors. Spermine (SPE) is an endogenous tetra-amine with excellent biocompatibility yet poor gene condensation capacity. We have previously synthesized a polyspermine based on SPE and poly(ethylene glycol) (PEG) diacrylate (SPE-alt-PEG) for enhanced transfection performance, but the synthesized SPE-alt-PEG still lacked specificity towards cancer cells. In this study, folic acid (FA) was incorporated into SPE-alt-PEG to fabricate a targeted gene delivery vector (FA-SPE-PEG) via an acylation reaction. FA-SPE-PEG exhibited mild cytotoxicity in both cancer cells and normal cells. FA-SPE-PEG possessed higher transfection efficiency than PEI 25 K and Lipofectamine(®) 2000 in two tested cancer cell lines at functional weight ratios, and its superiority over untargeted SPE-alt-PEG was prominent in cells with overexpressed folate receptors (FRs). Moreover, in vivo delivery of green fluorescent protein (GFP) with FA-SPE-PEG resulted in highest fluorescent signal intensity of all investigated groups. FA-SPE-PEG showed remarkably enhanced specificity towards cancer cells both in vivo and in vitro due to the interaction between FA and FRs. Taken together, FA-SPE-PEG was demonstrated to be a prospective targeted gene delivery vector with high transfection capacity and excellent biocompatibility.