Technical Breakthroughs and Safety Challenges of mRNA Vaccine Delivery Systems: Application and Optimization of Lipid Nanoparticles

This paper reviews the key technologies and research progress in mRNA vaccine delivery systems, with a particular focus on the pivotal role these systems play in enhancing mRNA stability, delivery efficiency, and safety. The effective delivery of mRNA relies on carrier systems, among which lipid nanoparticles (LNPs) have emerged as the most successful platform. LNPs form stable complexes by electrostatically binding ionizable lipids to mRNA, thereby protecting mRNA from degradation and facilitating cellular uptake. Various carrierssuch as cationic lipid nanoparticles, solid lipid nanoparticles (SLNs), and non-lamellar lipid nanoparticleseach exhibit distinct characteristics. However, the immunogenicity and toxicity of delivery systems present key challenges for clinical safety. Cationic lipids and polyethylene glycol (PEG) modifications may trigger inflammatory or allergic reactions, necessitating component optimization to reduce these risks. Moreover, the stability and targeting capabilities of delivery systems directly influence vaccine efficacy; PEGylation and auxiliary lipids can extend circulation time and minimize immune clearance. This paper systematically summarizes technological breakthroughs and existing issues in delivery systems, providing theoretical insights for the application of mRNA vaccines in infectious disease prevention and tumor immunotherapy.