Evaluation of pentaerythritol-based and trimethylolpropane-based cationic lipidic materials for gene delivery

Shuang Wu; Meiyan Liu; Xiang Hu; Chengxi He; Chunyan Zhao; Shuanglin Xiang; Youlin Zeng

doi:10.1016/j.bmcl.2022.128635

Evaluation of pentaerythritol-based and trimethylolpropane-based cationic lipidic materials for gene delivery

Bioorg Med Chem Lett. 2022 Apr 15:62:128635. doi: 10.1016/j.bmcl.2022.128635. Epub 2022 Feb 21.

Authors

Shuang Wu¹, Meiyan Liu¹, Xiang Hu², Chengxi He¹, Chunyan Zhao³, Shuanglin Xiang², Youlin Zeng⁴

Affiliations

¹ Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education of China), Hunan Normal University, Changsha 410081, PR China; Key Laboratory of the Assembly and Application of Organic Functional Molecules of Hunan Province, Hunan Normal University, Changsha 410081, PR China.
² Key Laboratory of Protein Chemistry and Developmental Biology of State Education Ministry of China, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, PR China.
³ Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education of China), Hunan Normal University, Changsha 410081, PR China.
⁴ Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education of China), Hunan Normal University, Changsha 410081, PR China; Key Laboratory of the Assembly and Application of Organic Functional Molecules of Hunan Province, Hunan Normal University, Changsha 410081, PR China. Electronic address: youlinzengcn@gmail.com.

PMID: 35202809
DOI: 10.1016/j.bmcl.2022.128635

Abstract

The chemical and physical structure of cationic liposomes pays an important effect on their gene transfection efficiency. Investigation on the structure-function relationship of cationic liposomes will guide the design of novel cationic liposomes with high transfection efficiency and biosafety. In this paper, two novel series of lipids based on the backbone of pentaerythritol and trimethylolpropane were discovered, and their gene transfection efficiencies were assayed in vitro. The four lipids 8c, 9c, 14b, and 15b, exhibited much better transfection efficiency in the HEK293 cell lines compared with Lipo2000, lipid 9c also showed good transfection efficiency in the SW480 cell lines. And the structure-efficiency relationship revealed that a hydroxyethyl polar head group boosted transfer potency in trimethylolpropane-type lipids, but reduced in pentaerythritol-type lipids.

Keywords: Cationic lipids; Gene delivery; Structure-efficiency relationship; Transfection efficiency.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cations / chemistry
DNA / chemistry
HEK293 Cells
Humans
Lipids* / chemistry
Lipids* / pharmacology
Liposomes* / chemistry
Propylene Glycols
Transfection

Substances

Cations
Lipids
Liposomes
Propylene Glycols
trimethylolpropane
DNA
pentaerythritol