Nanoplatform-Based Delivery Systems for Enhanced Stability and Efficacy of Nucleic Acid Vaccines

The rapid development of nucleic acid-based vaccines represents a major advancement in immunization strategies, characterized by their reliance on host cellular machinery to produce antigens. These third-generation platforms, including DNA and mRNA vaccines, offer key advantages such as rapid scalability, simplified manufacturing, and versatility in targeting a broad spectrum of diseases caused by infectious pathogens or conditions like cancer. While they avoid the use of live pathogens and thereby minimize many infection-related risks associated with pathogen reversion, potential side effects such as immune overactivation or off-target responses remain key safety considerations. Nanotechnology, particularly lipid nanoparticle (LNP) systems, has emerged as a critical enabler in addressing these limitations. LNPs enhance nucleic acid stability, promote cellular uptake, and facilitate targeted delivery, thereby improving both immune activation and overall safety profiles. Innovations in ionizable lipid design, PEGylation, and size-controlled formulations have been pivotal to the success of mRNA vaccines in response to the COVID-19 pandemic. This review focuses primarily on LNPs as delivery platforms, while also discussing emerging nanotechnologies under investigation in both preclinical and clinical settings. By examining advances in nanoparticle engineering, delivery strategies, and disease-specific applications, this review aims to provide a comprehensive overview of how nanotechnology is reshaping the future of nucleic acid vaccine development. This underscores the transformative potential of nanoscale delivery systems in overcoming current barriers and accelerating the innovation of next generation vaccines.