articleNature CommunicationsNov 2, 2024GOLD OA

Charge-assisted stabilization of lipid nanoparticles enables inhaled mRNA delivery for mucosal vaccination

Chinese Academy of Sciences · Beijing National Laboratory for Molecular Sciences · +4 more institutions

PubMed
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Abstract

Inhaled delivery of messenger RNA (mRNA) using lipid nanoparticle (LNP) holds immense promise for treating pulmonary diseases or serving as a mucosal vaccine. However, the unsatisfactory delivery efficacy caused by the disintegration and aggregation of LNP during nebulization represents a major obstacle. To address this, we develop a charge-assisted stabilization (CAS) strategy aimed at inducing electrostatic repulsions among LNPs to enhance their colloidal stability. By optimizing the surface charges using a peptide-lipid conjugate, the leading CAS-LNP demonstrates exceptional stability during nebulization, resulting in efficient pulmonary mRNA delivery in mouse, dog, and pig. Inhaled CAS-LNP primarily…

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