Lipid nanoparticles driving mRNA vaccine innovations: From concept to clinic

Messenger RNA (mRNA) vaccines have emerged as a transformative approach to immunization, driven by their ability to encode specific proteins that elicit targeted immune responses. However, the inherent instability of mRNA and its vulnerability to enzymatic degradation have necessitated the development of sophisticated delivery systems. This review explores the latest advancements in non-viral nanoparticle platforms-particularly lipid nanoparticles (LNPs), cationic liposomes, and lipid-polymer hybrids-for the efficient and safe delivery of mRNA. We analyze the structural and functional components of these nanoplatforms such as ionizable lipids, phospholipids, and PEGylated lipids, which enhance mRNA stability, circulation, and cellular uptake. Key challenges, including immunogenicity, cytotoxicity, and the "PEG dilemma" are examined alongside emerging solutions such as stimuli-responsive elements and targeted ligand modifications. Special emphasis is placed on microfluidic synthesis as a scalable production technique for generating uniform, clinically viable mRNA-loaded nanoparticles. By integrating insights from nanotechnology, immunology, and clinical medicine, this review highlights the critical innovations and ongoing challenges that shape the future of mRNA vaccine development. The conclusions drawn underscore the pivotal role of nanoparticle-based delivery systems in maximizing mRNA vaccine efficacy and advancing personalized immunization strategies against infectious diseases and cancer. ©