Structure and Morphology of Lipid Nanoparticles for Nucleic Acid Drug Delivery: A Review

Lipid nanoparticles (LNPs) are a clinically proven platform for protecting and delivering nucleic acid-based therapeutics. These multicomponent particles self-assemble into a core-shell structure with the nucleic acid cargo encapsulated in its core. Despite considerable research efforts to establish structure-efficacy relationships, their morphological and structural characteristics─particularly their internal composition and distribution─remain elusive. This uncertainty arises from several factors, including challenges in characterization, the dynamic nature of LNPs, sample heterogeneity, and poorly understood formulation-structure relationships. This review highlights the current state of research on the structure and morphology of LNPs, characterization techniques, and ongoing efforts to elucidate how formulation parameters affect the structural and morphological LNP properties.