mRNA Lipid Nanoparticle Delivery Systems: Composition, Optimization and Advances in Clinical Translation

Lipid nanoparticles (LNP) represent critical non‑viral carriers for mRNA delivery, capable of encapsulating, protecting mRNA, facilitating cellular uptake and enabling cytosolic release. This review summarizes the composition and delivery mechanisms of mRNA‑LNP. Optimization strategies including ionizable lipid structure, component ratio tuning, endosomal escape improvement and tissue‑targeted modification are analysed in depth. Its applications in vaccines, tumour therapy, protein replacement and gene‑editing are further outlined. Current bottlenecks contain limited endosomal‑escape efficiency, insufficient extra‑hepatic delivery, safety concerns for repeated administration, and consistency challenges in large‑scale manufacturing. Future efforts should focus on lipid‑structure and formulation optimization, alongside improved safety evaluation and quality‑control frameworks to accelerate clinical translation.