Nanocarrier-Based Systems for Targeted Delivery: Current Challenges and Future Directions.

Nanomaterials have become promising platforms in the field of drug and gene delivery, offering unique advantages over traditional therapeutic approaches. Their tunable physicochemical properties enable improved pharmacokinetics and therapeutic performance. A wide range of nanocarriers, including lipid-based, polymer-based, and hybrid systems, have been rapidly developed and are attracting increasing attention in both preclinical and clinical research. However, despite promising preclinical outcomes, these systems still encounter critical challenges in achieving precise delivery to specific tissues, cells, and intracellular compartments. This review provides a comprehensive assessment of recent advances in the design and application of nanocarriers for targeted delivery, with emphasis on strategies designed for nuclear targeting. In the context of nuclear targeting, it explores passive approaches involving modulation of particle size, morphology, and surface charge, alongside active targeting strategies incorporating nuclear localization signals and other ligands. In addition to highlighting progress, the review examines the limitations associated with delivery efficiency, off-target effects, and barriers to clinical translation. By addressing both advances and ongoing challenges, this review provides valuable insights into the design and engineering of targeted nanocarriers. These developments are crucial for unlocking the full potential of precision nanomedicine.