Cationic lipids from multi-component Passerini reaction for non-viral gene delivery: A structure-activity relationship study.
Bioorg Med Chem
; 100: 117635, 2024 Feb 15.
Article
in En
| MEDLINE
| ID: mdl-38340641
ABSTRACT
Although many types of cationic lipids have been developed as efficient gene vectors, the construction of lipid molecules with simple procedures remains challenging. Passerini reaction, as a classic multicomponent reaction, could directly give the α-acyloxycarboxamide products with biodegradable ester and amide bonds. Herein, two series of novel cationic lipids with heterocyclic pyrrolidine and piperidine as headgroups were synthesized through Passerini reaction (P-series) and amide condensation (A-series), and relevant structure-activity relationships on their gene delivery capability was studied. It was found that although both of the two series of lipids could form lipid nanoparticles (LNPs) which could effectively condense DNA, the LNP derived from P-series lipids showed higher transfection efficiency, serum tolerance, cellular uptake, and lower cytotoxicity. Unlike the A-series LNPs, the P-series LNPs showed quite different structure-activity relationship, in which the relative site of the secondary amine had significant effect on the transfection performance. The othro-isomers of the P-series lipids had lower cytotoxicity, but poor transfection efficiency, which was probably due to their unstable nature. Taken together, this study not only validated the feasibility of Passerini reaction for the construction of cationic lipids for gene delivery, but also afforded some clues for the rational design of effective non-viral lipidic gene vectors.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Gene Transfer Techniques
/
Lipids
Limits:
Humans
Language:
En
Journal:
Bioorg Med Chem
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2024
Document type:
Article