Delivery of small interfering ribonucleic acid using lipid nanoparticles prepared with pH-responsive dipeptide-conjugated lipids.
Biochem Biophys Res Commun
; 729: 150372, 2024 Oct 15.
Article
en En
| MEDLINE
| ID: mdl-38981400
ABSTRACT
The development of lipid nanoparticles (LNPs) has enabled the clinical application of small interfering ribonucleic acid (siRNA)-based therapies. Accordingly, various unique ionizable lipids have been explored for efficient siRNA delivery. However, safety concerns related to the structure of ionizable lipids have been raised. Here, we developed a pH-responsive dipeptide-conjugated lipid (DPL) for efficient, high safety siRNA delivery. We synthesized a DPL library by varying the dipeptide sequence and established a strong correlation between the knockdown efficiency of the DPL-based LNPs and the dipeptide sequence. The LNPs prepared with a DPL containing arginine (R) and glutamic acid (E) (DPL-ER) exhibited the highest knockdown efficiency. In addition, the DPL-ER-based LNPs with relatively long lipid tails (DPL-ER-C22C22) exhibited a higher knockdown efficiency than those with short ones (DPL-ER-18C18). The zeta potential of the DPL-ER-C22C22-based LNPs increased as the pH decreased from 7.4 (physiological condition) to 5.5 (endosomal condition). Importantly, the DPL-ER-C22C22-based LNPs exhibited a higher knockdown efficiency than the LNPs prepared using commercially available ionizable lipids. These results suggest that the DPL-based LNPs are safe and efficient siRNA delivery carriers.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
ARN Interferente Pequeño
/
Dipéptidos
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Nanopartículas
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Lípidos
Límite:
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2024
Tipo del documento:
Article
País de afiliación:
Japón