Helper-Polymer Based Five-Element Nanoparticles (FNPs) for Lung-Specific mRNA Delivery with Long-Term Stability after Lyophilization.
Nano Lett
; 22(16): 6580-6589, 2022 08 24.
Article
em En
| MEDLINE
| ID: mdl-35969167
ABSTRACT
Lipid nanoparticles (LNPs) carrying therapeutic mRNAs hold great promise in treating lung-associated diseases like viral infections, tumors, and genetic disorders. However, because of their thermodynamically unstable nature, traditional LNPs carrying mRNAs need to be stored at low temperatures, which hinders their prevalence. Herein, an efficient lung-specific mRNA delivery platform named five-element nanoparticles (FNPs) is developed in which helper-polymer poly(ß-amino esters) (PBAEs) and DOTAP are used in combination. The new strategy endows FNPs with high stability by increasing the charge repulsion between nanoparticles and the binding force of the aliphatic chains within the nanoparticles. The structure-activity relationship (SAR) shows that PBAEs with E1 end-caps, higher degrees of polymerization, and longer alkyl side chains exhibit higher hit rates. Lyophilized FNP formulations can be stably stored at 4 °C for at least 6 months. Overall, a novel delivery platform with high efficiency, specificity, and stability was developed for advancing mRNA-based therapies for lung-associated diseases.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polímeros
/
Nanopartículas
Tipo de estudo:
Risk_factors_studies
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article