Distinct Endocytic Pathways Affect Transfection Efficiency of SORT Lipid Nanoparticles

Adam Fajriawan – PhD student, University of Groningen; Anna Salvati – Associate Professor, University of Groningen

Introduction:

Achieving extra-hepatic targeting remains a pivotal challenge in LNP-therapeutics. While Selective Organ Targeting (SORT) LNPs enable tissue-specific tropism via inclusion of a charged lipid [1, 2], some aspects of their intracellular behavior remain poorly characterized. Herein, we investigate how LNP charge and the resulting biomolecular corona modulate endocytic pathways and transfection efficiency of SORT LNPs. By using selective pharmacological inhibition, we characterized the internalization mechanisms of the different LNPs and determined how distinct mechanisms affect transfection.