Glycan Chemical Structures Dictate Organ- and Cell-Specific Tropism and Immunomodulation of Lipid Nanoparticles

T cells, the latter being a critical yet rarely achieved response in standard LNP formulations. A head-to-head comparison showed that intravenous (IV) administration of our glycan-LNP vaccines resulted in improved tumor control compared with the benchmark intramuscular (IM) formulation. Moreover, they induce minimal cytokine release in human peripheral blood mononuclear cells, underscoring their translational potential. Together, these findings establish glycan chemistry as a tunable and generalizable design parameter for controlling mRNA nanoparticle biodistribution and immune engagement, providing a framework for the rational engineering of targeted mRNA delivery systems.