Pulmonary Delivery of Hybrid Polymeric Nanoparticles for Enhanced mRNA Expression
Min Jiang1, Felix Sieber-Schäfer1, Simone P. Carneiro1, Olivia M. Merkel1,2*
1Department of Pharmacy, Ludwig-Maximilians-University Munich, Butenandtstrasse 5-13, Haus B, 81377 Munich, Germany
2Center for NanoScience (CeNS), Ludwig-Maximilians-University Munich, 80799 Munich, Germany
Summary
Recent advances in the field of mRNA vaccination have demonstrated significant advantages in activating immune responses and combating infectious diseases. However, many pathogens and viruses, including SARS-CoV-2, primarily infect the host through the respiratory tract. Conventional vaccines administered via non-respiratory routes usually fail to induce protective mucosal immunity, which limits the elimination of pathogens and viruses at the first entry site and still results in the risk of acute infection. Therefore, we aimed to develop a pulmonary mRNA nanovaccine capable of achieving both crucial mucosal immunity and systemic immunity against infectious diseases. To accomplish this, we have innovatively designed a hybrid nanoplatform based on a non-lipid system, integrating biodegradable poly(lactide-co-glycolide) (PLGA) and poly (β-amino esters) (PBAEs) into nanoscale core-shell particles for loading and delivering mRNA. The mRNA-loaded hybrid nanoparticles had an average size of 198.8 ± 4.4 nm and exhibited a slightly positive charge in 10mM pH7.4 HEPES buffer. Through evaluation of the post-transfection effects of eGFP-mRNA on both dendritic cells and lung epithelial cells, we have confirmed the superiority of the nanohybrid system in mRNA delivery compared to the PBAE-based nanopolyplex system used alone. This enhanced delivery efficiency can be attributed to the optimized structure, enhanced hydrophobicity and improved stability of the hybrid nanoparticles, which will be further explored in future research.