Synthesis of a novel adapter lipid using Fc-region mediated antibody modification for post-insert preparation of transferrin receptor targeted messenger RNA-loaded lipid nanoparticles.
Eur J Pharm Biopharm
; : 114468, 2024 Aug 20.
Article
em En
| MEDLINE
| ID: mdl-39173936
ABSTRACT
Lipid nanoparticles (LNPs) are promising delivery systems with the ability to deliver small interfering RNA (siRNA) and messenger RNA (mRNA) in diseased tissues and intracellular sites of action. However, delivery to non-hepatic tissues via systemic administration remains challenging. Antibody modification of LNPs is a hopeful approach for improving their selectivity to target tissues. The conventional method of antibody modification via thiol-maleimide linkage is concerned with reduced recognition efficiency of the disease-related target molecules owing to variations in antibody orientation on the surface of the LNPs. In this study, we developed a novel adapter lipopeptide for antibody modification of LNPs via the Fc-region. Here, we selected RI7-217, an anti-transferrin receptor antibody, as the ligand. Through optimization of spacer peptides, we found a FcBP-EKGG-lipid exhibits high water-dispersibility for post-insertion method to LNPs. We prepared RI7-217-modified LNPs by modifying LNPs with FcBP-EKGG-lipids and mixing the antibodies. We found that the luciferase protein expression of RI7-217-modified LNPs was significantly enhanced in an antibody-specific manner against transferrin receptor-expressing U-87 MG cells. This information would be valuable in the development of antibody-modified LNPs for cell-selective targeting.
Texto completo:
1
Base de dados:
MEDLINE
Idioma:
En
Revista:
Eur J Pharm Biopharm
Assunto da revista:
FARMACIA
/
FARMACOLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Japão