Optimal delivery strategies for nanoparticle-mediated mRNA delivery

Messenger RNA (mRNA) has emerged as a new and efficient agent for the treatment of various diseases. The success of lipid nanoparticle-mRNA against the novel coronavirus (SARS-CoV-2) pneumonia epidemic has proved the clinical potential of nanoparticle-mRNA formulations. However, the deficiency in the effective biological distribution, high transfection efficiency and good biosafety are still the major challenges in clinical translation of nanomedicine for mRNA delivery. To date, a variety of promising nanoparticles have been constructed and then gradually optimized to facilitate the effective biodistribution of carriers and efficient mRNA delivery. In this review, we describe the design of nanoparticles with an emphasis on lipid nanoparticles, and discuss the manipulation strategies for nanoparticle-biology (nano-bio) interactions for mRNA delivery to overcome the biological barriers and improve the delivery efficiency, because the specific nano-bio interaction of nanoparticles usually remoulds the biomedical and physiological properties of the nanoparticles especially the biodistribution, mechanism of cellular internalization and immune response. Finally, we give a perspective for the future applications of this promising technology. We believe that the regulation of nano-bio interactions would be a significant breakthrough to improve the mRNA delivery efficiency and cross biological barriers. This review may provide a new direction for the design of nanoparticle-mediated mRNA delivery systems.