Zwitterionic Polymer-Decorated Lipid Nanoparticles for mRNA Delivery in Mammalian Cells.
Biomacromolecules
; 24(12): 5654-5665, 2023 12 11.
Article
en En
| MEDLINE
| ID: mdl-37956106
ABSTRACT
Lipid nanoparticles (LNPs) play a key role in the effective transport of mRNA into cells for protein translation. Despite the stealthiness of poly(ethylene glycol) (PEG) that helps protect LNPs from protein absorption and blood clearance, the generation of anti-PEG antibodies resulting in PEG allergies remains a challenge for the development of an mRNA vaccine. Herein, a non-PEG lipid was developed by conjugating 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE) with an antifouling zwitterionic polymer, poly(2-methyacryloyloxyethyl phosphorylcholine) (PMPC), of different chain lengths. The PMPC-LNPs formulated from DPPE-PMPC were spherical (diameter ≈ 144-255 nm), neutral in charge, and stable at 4 °C for up to 28 days. Their fraction of stealthiness being close to 1 emphasized the antifouling characteristics of PMPC decorated on LNPs. The PMPC-LNPs were nontoxic to HEK293T cells, did not induce inflammatory responses in THP-1 cells, and exhibited an mRNA transfection efficiency superior to that of PEG-LNPs. This work demonstrated the potential of the developed zwitterionic polymer-conjugated LNPs as promising mRNA carriers.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Polímeros
/
Nanopartículas
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Biomacromolecules
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2023
Tipo del documento:
Article
País de afiliación:
Tailandia