摘要Lipid nanoparticles(LNPs)have emerged as versatile carriers for the delivery of genetic medicines and small-molecule drugs,offering desired benefits for therapeutic applications.Optimization of the treatment efficacy of nanocarriers necessitates a thorough understanding of the connection between pharmacokinetics and physicochemical properties.This review consolidates scientific efforts to elucidate how LNP's physicochemical attributes influence their in vivo fate,emphasizing particle size and shape,surface electric potential and ligand-binding chemistry.By examining the interplay between LNPs and biological barriers across various administration routes,this review provides insights into tailoring LNP properties for optimal delivery and reduced off-target effects.Recommendations for future research are provided to advance the study of LNP in vivo behaviors and offer a practical framework for optimizing in vivo performance through product design parameters.