Lipid Nanoparticles at the Crossroads of Chemistry and Medicine: A Tutorial

Abstract

Lipid nanoparticles (LNPs) have risen to the forefront of modern therapeutics by enabling the clinical success of COVID-19 mRNA vaccines. In order for them to function as drug delivery vesicles, LNPs must have scalable, tunable, and targeted nanoscale platforms whose strengths in versatility, performance, and clinical relevance are driven by key design parameters and formulation strategies. This Tutorial Review traces the historical evolution of LNPs and examines the fundamental design principles governing their structure, physicochemical properties, and biological behavior. It further highlights modern analytical characterization techniques that have advanced mechanistic understanding of LNP composition, morphology, and function as well as targeting strategies to improve LNP delivery to extrahepatic sites. Current translational challenges and emerging advances are also discussed. This Tutorial Review provides a framework for understanding the foundations, current landscape, and future directions of LNP research.