Kidney-targeted nanoplatforms: Strategies and applications

Renal diseases remain a major global health burden, with an estimated 850 million individuals affected by chronic kidney disease, acute kidney injury, glomerulonephritis, and diabetic nephropathy. These multifactorial diseases collectively account for substantial morbidity and mortality burdens. This grim trajectory demands urgent development of drugs that are capable of simultaneously enhancing renal efficacy while circumventing systemic toxicity. In response to this challenge, engineered nanoplatforms designed specifically for the treatment of kidney diseases have emerged as a promising solution. These nanoplatforms offer the unique ability to deliver targeted therapeutics directly to specific regions of the kidney, thereby improving drug efficacy while reducing off-target effects. Unlike the well-established oncological applications of nanomedicine, renal-specific formulations remain in their developmental nascency. Nevertheless, accumulating preclinical evidence indicates that nanotherapeutics hold significant promise for improving the clinical management of kidney diseases through targeted and mechanism-based interventions. The nephrotropic mechanisms and structural determinants of renal nanoplatforms fundamentally diverge from those of conventional nanotherapeutics. Therefore, a thorough understanding of the principles governing renal targeting is essential for designing nanomedicines that achieve precise kidney-specific delivery while ensuring biosafety. In this review, we summarize the current understanding of structure-function relationships that govern the targeting efficiency and biodistribution of nanoparticles in the kidney, with a focus on passive targeting mechanisms driven by key physicochemical parameters, such as particle size, surface charge, shape, and density, as well as active targeting strategies based on specific receptor-ligand interactions.