Abstract
To improve lipid nanoparticle (LNP)-mediated delivery to nonliver tissues, scientists modify LNP chemistry or add targeting ligands. One underexplored alternative is to change the formulation process that creates the LNP. Here, we report that an LNP formulated with a herringbone mixer led to 2-fold more heart delivery than the same LNP formulated with a bifurcating mixer. The two LNPs had similar biophysical traits, yet they adsorbed different protein coronas, suggesting that the effect was driven by systemic physiology. By using spatial transcriptomics to track LNP delivery in a mouse model of atherosclerosis, we found that the improved LNP delivered mRNA to diseased regions and cardiomyocytes after an intravenous injection. These data suggest that it is possible to increase heart delivery via nanoparticle processing.