Therapeutic Implications of Biomolecular Corona on Lipid Nanoparticle-Based Gene Delivery Systems

Lipid nanoparticles (LNPs) are widely used in drug delivery due to their low toxicity, excellent biocompatibility, and ability to facilitate endosomal escape. A critical factor influencing the in vivo behavior of LNPs is the formation of a biomolecular corona (BC) on their surface. This layer of biomolecules affects key biological processes such as targeting, absorption, distribution, metabolism, and clearance. Gaining a deeper understanding of the BC formation mechanisms is essential for predicting and optimizing the therapeutic efficacy of LNPs. In this perspective, we present recent advances in the characterization, isolation, and functional implications of the BC. We explore how BC formation affects the stability, biodistribution, and targeting capacity of LNPs, and discuss how harnessing this phenomenon could offer a powerful strategy to improve the precision and effectiveness of targeted drug delivery.