ABSTRACT
Nucleic acid-based therapeutics hold great promise for the treatment of human diseases such as cancer. Lipid nanoparticles (LNPs) can be produced easily and clinical trials have already shown the potential safety and effectiveness of this class of carriers in humans. To achieve even higher specificity, LNPs can be surface modified with ligands that specifically recognize receptors on tumor cells. Lipid nanoparticles have been recognized as one of the most promising delivery systems mainly due to their biocompatibility and relatively ease of large-scale production. Moreover, early clinical trials have demonstrated the potential safety and efficacy of these systems. Neutral lipids, including egg phosphatidylcholine, cholesterol, and dioleoyl-phosphatidyletha-nolamine (DOPE), are used to improve the stability of the LNPs or, in the case of DOPE, to promote endosomal escape. The process of endosomal membrane destabilization is associated with the structural evolution of lipoplexes/anionic lipids from a stable bilayer phase to an unstable phase.
