NANOMEDICINE AND LIPID NANOPARTICLES: TARGETED DELIVERY OF NUCLEIC ACIDS AND SMALL MOLECULES IN ONCOLOGY AND BEYOND

Nanomedicine has transformed drug delivery by enabling the encapsulation, protection, and targeted release of therapeutic agents, particularly nucleic acids and small molecules. Among nanocarrier systems, lipid nanoparticles have emerged as the leading platform for nucleic acid delivery, largely due to the clinical success of mRNA vaccines against COVID-19 and the FDA approval of patisiran, a lipid nanoparticle-formulated siRNA for hereditary transthyretin amyloidosis. Lipid nanoparticles typically consist of ionizable cationic lipids, cholesterol, helper phospholipids, and PEGylated lipids, which together facilitate efficient encapsulation, cellular uptake, and endosomal escape. This review critically examines the design principles, mechanisms, and clinical applications of lipid nanoparticles in oncology and other disease areas, focusing on literature published through 2024. In oncology, lipid nanoparticles are being used for mRNA cancer vaccines, siRNA-mediated gene silencing, and delivery of small-molecule chemotherapeutics. Targeted delivery strategies, including ligand conjugation and stimuli-responsive formulations, aim to improve tumor specificity and reduce systemic toxicity. Beyond oncology, lipid nanoparticles have enabled hepatic gene silencing, infectious disease vaccines, and emerging applications in rare metabolic and cardiovascular diseases. Challenges remain, including immunogenicity, off-target hepatic accumulation, manufacturing scalability, and long-term safety. Future directions include next-generation ionizable lipids, extrahepatic targeting, and combination therapies. Overall, lipid nanoparticles represent a versatile and clinically validated platform that is poised to expand the therapeutic landscape.