2. Academic Validation
  3. Skeleton-Controlled pDNA Delivery of Renewable Steroid-Based Cationic Lipids, the Endocytosis Pathway Analysis and Intracellular Localization

Skeleton-Controlled pDNA Delivery of Renewable Steroid-Based Cationic Lipids, the Endocytosis Pathway Analysis and Intracellular Localization

  • Int J Mol Sci. 2018 Jan 26;19(2):369. doi: 10.3390/ijms19020369.
Ruilong Sheng 1 2 3,  Zhao Wang 4,  Ting Luo 5,  Amin Cao 6,  Jingjing Sun 7,  Joseph M Kinsella 8
Affiliations

Affiliations

  • 1 Key Laboratory of Synthetic and Self-Assembly Chemistry for Organic Functional Molecules, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Lingling Road 345, Shanghai 200032, China. ruilong.sheng@staff.uma.pt.
  • 2 Department of Bioengineering, McGill University, 817 Sherbrook Street, Montréal, QC H3A0C3, Canada. ruilong.sheng@staff.uma.pt.
  • 3 CQM-Centro de Química da Madeira, Universidade da Madeira, Campus da Penteada, 9000-390 Funchal, Portugal. ruilong.sheng@staff.uma.pt.
  • 4 Key Laboratory of Synthetic and Self-Assembly Chemistry for Organic Functional Molecules, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Lingling Road 345, Shanghai 200032, China. wangzhaosioc@163.com.
  • 5 Key Laboratory of Synthetic and Self-Assembly Chemistry for Organic Functional Molecules, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Lingling Road 345, Shanghai 200032, China. luoting@sioc.ac.cn.
  • 6 Key Laboratory of Synthetic and Self-Assembly Chemistry for Organic Functional Molecules, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Lingling Road 345, Shanghai 200032, China. acao@mail.sioc.ac.cn.
  • 7 Key Laboratory of Synthetic and Self-Assembly Chemistry for Organic Functional Molecules, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Lingling Road 345, Shanghai 200032, China. feliciasun23@gmail.com.
  • 8 Department of Bioengineering, McGill University, 817 Sherbrook Street, Montréal, QC H3A0C3, Canada. joseph.kinsella@mcgill.ca.
PMID: 29373505 DOI: 10.3390/ijms19020369
Abstract

Using renewable and biocompatible natural-based resources to construct functional biomaterials has attracted great attention in recent years. In this work, we successfully prepared a series of steroid-based Cationic Lipids by integrating various steroid skeletons/hydrophobes with (l-)-arginine headgroups via facile and efficient synthetic approach. The plasmid DNA (pDNA) binding affinity of the steroid-based Cationic Lipids, average particle sizes, surface potentials, morphologies and stability of the steroid-based Cationic Lipids/pDNA lipoplexes were disclosed to depend largely on the steroid skeletons. Cellular evaluation results revealed that cytotoxicity and gene transfection efficiency of the steroid-based Cationic Lipids in H1299 and HeLa cells strongly relied on the steroid hydrophobes. Interestingly, the steroid lipids/pDNA lipoplexes inclined to enter H1299 cells mainly through caveolae and lipid-raft mediated endocytosis pathways, and an intracellular trafficking route of "lipid-raft-mediated endocytosis→lysosome→cell nucleic localization" was accordingly proposed. The study provided possible approach for developing high-performance steroid-based lipid gene carriers, in which the cytotoxicity, gene transfection capability, endocytosis pathways, and intracellular trafficking/localization manners could be tuned/controlled by introducing proper steroid skeletons/hydrophobes. Noteworthy, among the lipids, Cho-Arg showed remarkably high gene transfection efficacy, even under high serum concentration (50% fetal bovine serum), making it an efficient gene transfection agent for practical application.

Keywords

endocytosis pathway; gene delivery; serum-compatible; steroid; structure–function relationships.

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