Sub-15 nm Nanoparticles for Drug Delivery: Emerging Frontiers and Therapeutic Potential

Nanoparticles (NPs) have significantly changed the field of drug delivery, offering control over pharmacokinetics, biodistribution, and targeted therapy. Among these, ultrasmall nanoparticles (USNPs) with sizes of approximately 5-15 nm have garnered significant interest due to their unique physicochemical properties, including enhanced cellular uptake, deeper tissue penetration, and prolonged systemic circulation. This review explores the fundamental principles governing sub-15 nm nanoparticles, their classification, and their distinctive advantages in pharmaceutical applications. Various types of nanoparticles, including polymeric, lipid-based, metallic, and carbon-based nanosystems, are examined in the context of drug delivery in cancer therapy. We detail how sub-15 nm polymeric nanoparticles (PNPs) are emerging as transformative drug delivery platforms for cancer therapy. The impact of nanoparticle size, surface modifications, and biocompatibility on therapeutic performance is critically analyzed. Furthermore, we discuss emerging applications of these ultrasmall nanoparticles in cancer therapy, neurological disorders, vaccine delivery, and imaging. Despite their promise, key challenges such as stability, aggregation, toxicity, and regulatory concerns remain significant hurdles for clinical translation. This review provides insights into the potential of 5-15 nm nanoparticles to reshape modern drug delivery and highlights future directions for research and development in this rapidly evolving field.