(179) PEGylated siRNA loaded LNPs with enhanced cytosolic release

Introduction: Lipid nanoparticles (LNPs) are effective nucleic acid delivery systems due to their customizable lipid composition. Cationic/ionizable lipids aid in loading nucleic acids, while fusogenic lipids enhance endosomal escape (1). PEGylation improves stability and circulation time but can hinder cellular uptake and endosomal escape, known as the "PEG dilemma." To overcome this, targeting agents ensure specific cell uptake, and pH-sheddable PEG-lipids enable unshielding in endosomal conditions, enhancing intracellular release in target cells (2).