Rewriting the mRNA Delivery Map: Albumin Hitchhiking Lipid Nanoparticles for Safer and Smarter Nanomedicine

LNPs are the basis of mRNA and nucleic acid-based therapeutics. However, their remarkable clinical potential is limited by a persistent challenge, i.e., nonspecific accumulation in the liver and associated hepatotoxicity. Traditional strategies, such as PEGylation and lipid ionization modification, have reached a point of low therapeutic value-add to control biodistribution. Recently published studies present an innovative concept: LNPs that recruit albumin, exploiting interactions with endogenous albumin to avoid liver accumulation and simultaneously improve delivery through the lymphatic system for immune-modulation. This review provides a concise incursion into such strategies that redefine stealth nanomedicine, not as chemical camouflage but as a biological alliance with plasma transport proteins, paving the way for a new paradigm of self-protecting nanocarriers for safer and more precise mRNA therapeutics.