LIPID NANOPARTICLES: BIOPHYSICAL SOLUTIONS FOR BIOMEDICAL PROBLEMS

Lipid nanoparticles (LNPs) have emerged as a cutting-edge platform for drug delivery and gene therapy, offering solutions to a range of biomedical challenges. It is well known that the biocompatibility of LNPs and their ability to encapsulate hydrophobic and hydrophilic molecules are intrinsically related to the biophysical characteristics of each type of LNP. Furthermore, LNPs interact with biological barriers mainly through electrostatic interactions, membrane fusion, and/or receptor-mediated endocytosis, and their biophysical properties also influence immune evasion and penetration of barriers such as the blood-brain barrier. Despite their immense potential, challenges remain in optimizing LNP formulations for patient-specific applications. Biophysical factors such as lipid composition, particle charge, membrane organization, and stability in biological fluids must be finely tuned to enhance therapeutic efficacy and minimize off-target effects. Here, we explore how the optimization of these biophysical properties enhances cellular uptake and targeted biodistribution, in addition to modulating the immune system for improved therapeutic outcomes. We also present state-of-the-art results on LNPs, specifically biomimetic lipid nanoparticles, highlighting the opportunities these nanoparticles present as a tool for personalized medicine, targeted therapies, vaccine development, and the treatment of complex diseases.