AI Article Synopsis
- - The study focuses on improving the inhaled delivery of mRNA using lipid nanoparticles (LNP), which face challenges like disintegration and aggregation during nebulization, hindering treatment effectiveness for lung diseases and mucosal vaccines.
- - A new strategy called charge-assisted stabilization (CAS) enhances LNP stability by creating electrostatic repulsions, leading to better mRNA delivery in animal models (mouse, dog, and pig).
- - The effective delivery of inhaled CAS-LNP triggers strong immune responses and shows potential as a vaccine against the SARS-CoV-2 Omicron variant, as well as for cancer treatment to reduce lung metastasis.
Article 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 transfect dendritic cells, triggering robust mucosal and systemic immune responses. We demonstrate the efficacy of inhaled CAS-LNP as a vaccine for SARS-CoV-2 Omicron variant and as a cancer vaccine to inhibit lung metastasis. Our findings illustrate the design principles of nebulized LNPs, paving the way of developing inhaled mRNA vaccines and therapeutics.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531489 | PMC |
| http://dx.doi.org/10.1038/s41467-024-53914-x | DOI Listing |
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