Cationic Nanoparticles Assembled from Natural-Based Steroid Lipid for Improved Intracellular Transport of siRNA and pDNA.
Developing new functional biomaterials from biocompatible natural-based resources for gene/drug delivery has attracted increasing attention in recent years. In this work, we prepared a series of cationic nanoparticles (Diosarg-DOPE NPs) by assembly of a natural steroid diosgenin-based cationic lipid (Diosarg) with commercially-available helper lipid 1,2-dioleoyl-sn-glycero-3-phosphorethanolamine (DOPE). These cationic Diosarg-DOPE NPs were able to efficiently bind siRNA and plasmid DNA (pDNA) via electrostatic interactions to form stable, nano-sized cationic lipid nanoparticles instead of lamellar vesicles in aqueous solution. The average particle size, zeta potentials and morphologies of the siRNA and pDNA complexes of the Diosarg-DOPE NPs were examined. Thein vitrocytotoxicity of NPs depends on the dose and assembly ratio of the Diosarg and DOPE. Notably, the intracellular transportation efficacy of the exogenesis siRNA and pDNA could be greatly improved by using the Diosarg-DOPE NPs as the cargoes in H1299 cell line. The results demonstrated that the self-assembled Diosarg-DOPE NPs could achieve much higher intracellular transport efficiency for siRNA or pDNA than the cationic lipid Diosarg, indicating that the synergetic effect of different functional lipid components may benefit the development of high efficiency nano-scaled gene carriers. Moreover, it could be noted that the traditional "lysosome localization" involved in the intracellular trafficking of the Diosarg and Diosarg-DOPE NPs, indicating the co-assembly of helper lipid DOPE, might not significantly affect the intracellular localization features of the cationic lipids.
CAS Key Laboratory for Organic Functional Materials, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China. rlsheng@mail.sioc.ac.cn.|Department of Chemistry, Université de Montréal, C.P.6128, Succursale Centre-ville, Montréal, QC H3C3J7, Canada. rlsheng@mail.sioc.ac.cn.
Ruilong
R
Sheng
General Hospital of Ningxia Medical University, Yinchuan 750004, China. zhuangxiaoqing@gmail.com.
Xiaoqing
X
Zhuang
CAS Key Laboratory for Organic Functional Materials, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China. wangz@mail.sioc.ac.cn.
Zhao
Z
Wang
CAS Key Laboratory for Organic Functional Materials, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China. acao@mail.sioc.ac.cn.
Amin
A
Cao
School & Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, 399 Middle Yanchang Road, Shanghai 200072, China. lklecnu@aliyun.com.
Kaili
K
Lin
Department of Chemistry, Université de Montréal, C.P.6128, Succursale Centre-ville, Montréal, QC H3C3J7, Canada. julian.zhu@umontreal.ca.
Julian X X
JX
Zhu
diosgenin; intracellular uptake; pDNA; siRNA; steroid