Precision Nanomedicine for Renal Tubular Injury: From Passive Accumulation to Subcellular Targeting

Renal tubular epithelial cell injury is a central pathogenic feature of kidney diseases, yet precise therapeutic interventions remain elusive. Conventional nanomedicines relying on passive accumulation lack the specificity required to treat complex tubular pathologies. This review elucidates the evolution of renal nanotherapeutics from non-specific organ accumulation to active, biologically informed targeting. We examine strategies utilizing specific surface receptors and injury-associated microenvironmental signals to engineer ligand-directed and stimuli-responsive nanocarriers. Furthermore, we highlight biomimetic platforms, such as engineered extracellular vesicles. Crucially, to achieve the ultimate goal of precision intervention, we emphasize the necessity of subcellular targeting. With a primary focus on mitochondria, we delineate hierarchical delivery strategies designed to restore cellular bioenergetics and metabolic homeostasis. Finally, we provide a forward-looking perspective on overcoming translational barriers by integrating DNA barcoding and artificial intelligence to accelerate the discovery of clinically translatable, precision nanomedicines.