Engineering strategies and translational progress in targeted nanoparticle drug delivery

INTRODUCTION: Nanoparticle-based drug delivery has emerged as a transformative approach in modern therapeutics, offering improved targeting efficiency, enhanced pharmacokinetics, and reduced systemic toxicity compared to conventional drug delivery systems. AREAS COVERED: This review comprehensively examines major nanocarrier platforms, including lipid-based, polymeric, inorganic, and hybrid systems, with emphasis on their structural design and functional properties. It further explores current advancements in targeting strategies, including passive targeting via the enhanced permeability and retention (EPR) effect and active targeting through ligand-receptor interactions involving antibodies, peptides, aptamers, and small molecules. Key biological and technological barriers to clinical translation are also discussed, such as tumor heterogeneity, abnormal vasculature, dense extracellular matrix, immune clearance, and limited cellular uptake. Additionally, emerging stimuli-responsive systems, including pH-, redox-, and enzyme-sensitive nanocarriers, are highlighted for their role in controlled and site-specific drug release. EXPERT OPINION/COMMENTARY: Despite significant progress, the clinical translation of nanomedicine remains constrained by biological complexities and scalability challenges. Future advancements integrating biomimetic strategies, multifunctional design, and artificial intelligence-driven modeling are expected to enhance targeting precision, biocompatibility, and translational success.