Pulmonary surfactant camouflage lipid nanoparticles for efficient mRNA lung delivery

Lipid nanoparticles (LNPs)-based mRNA vaccines have played a pivotal role in curbing the Corona Virus Disease 2019 (COVID-19) pandemic and transformed the field of vaccine development. 1 Inhaled vaccines, which can activate mucosal immunity in the respiratory tract, are capable of establishing protection at the first line of defense against viral infections. 2 However, to date, no inhaled mRNA-LNP vaccine has successfully completed clinical trials. One critical factor contributing to the inconsistent efficacy of inhaled mRNA vaccines lies in the structural complexity of the respiratory mucosal barrier, which poses significant obstructions to nanoparticle delivery. 3 Therefore, there is an urgent need to develop LNPs with mucosal residence and penetration capabilities to advance the clinical application of inhaled mRNA vaccines.