Cancer remains a significant global health burden, and the limitations of conventional anticancer therapies have driven the development of innovative nanotechnology-based drug delivery systems. Challenges including inadequate tumor selectivity, systemic toxicity, multidrug resistance, and insufficient therapeutic efficacy have highlighted the need for more precise treatment strategies. Smart targeted nanoparticles have emerged as promising delivery platforms because they combine selective tumor targeting, controlled drug release, prolonged circulation, and multifunctional therapeutic functions.
This review summarizes recent advances in smart nanoparticle-mediated drug delivery for precision oncology. It discusses the fundamental concepts of targeted cancer therapy and examines the major physiological and biological barriers affecting nanoparticle transport, particularly the tumor microenvironment and the limitations of the enhanced permeability and retention (EPR) effect. Additionally, the structural characteristics, biomedical applications, and therapeutic potential of lipid-based, polymeric, inorganic, hybrid, and biomimetic nanoparticles are evaluated. Recent progress in passive and active targeting, ligand-, antibody-, peptide-, and aptamer-mediated delivery, stimuli-responsive nanocarriers, and surface engineering strategies designed to improve tumor specificity and therapeutic outcomes is also discussed.
In addition, current preclinical and clinical developments, biosafety concerns, regulatory considerations, and challenges associated with large-scale manufacturing and clinical translation are comprehensively evaluated. Finally, emerging technologies, including artificial intelligence-assisted nanoparticle design, theranostic nanoplatforms, RNA therapeutics, gene editing, and personalized nanomedicine, are discussed as future directions for improving the efficacy, safety, and clinical applicability of smart targeted nanoparticles. Collectively, these advances position smart nanomedicine as a transformative strategy for achieving personalized and precision cancer therapy.