A recent study from Chandra Bhattacharya's (Chemistry and Biochemistry) laboratory developed a lipid nanoparticle platform that can deliver mRNA intravenously to the spleen with 99% selectivity. This work was published in Small, titled "Endogenous Corticosteroid Derived Lipid Nanoparticles (Cortico LNPs) Enable Selective mRNA Delivery to the Spleen.''

Abstract: In this study, we introduce a new class of lipid nanoparticles (LNPs), endogenous corticosteroid-derived LNPs (cortico-LNPs), in which the cholesterol component is replaced with endogenous corticosteroids, resulting in redirection from the liver to the spleen. Specifically, corticosterone- and progesterone-based LNPs achieve remarkable spleen selectivity of 97% and 99%, respectively, while maintaining robust protein expression in vivo. These cortico-LNPs also exhibit improved safety profiles compared to the clinical benchmark SM-102 formulation. Mechanistically, we propose that β2-glycoprotein I (β2-GPI) adsorption on the LNP surface mediates spleen-specific delivery. Importantly, this corticosteroid modification strategy is compatible with multiple clinically approved ionizable lipids, including MC3 and ALC-0315, highlighting its versatility across LNP platforms. Our findings underscore the potential of cortico-LNPs to reprogram organ tropism and expand the scope of precision gene and immunotherapies beyond the liver.