Nanotechnology-mediated podocyte injury repair: mechanistic exploration and therapeutic prospects

Podocyte injury serves as a central pathological driver in chronic kidney diseases (CKD), including diabetic kidney disease (DKD) and IgA nephropathy (IgAN). However, conventional therapies are still limited by poor targeting efficacy and systemic side effects. Nanotechnology provides transformative strategies via tunable nanomedicines, which enables precise podocyte repair through targeted drug delivery, antioxidant and anti-inflammatory effects, as well as gene regulation. This review exclusively focuses on the preclinical research progress in this field. Three categories of nanomaterials: peptide-drug conjugates (PDCs), polymeric nanoparticles (PNs), and inorganic nanomaterials (INs), exhibit distinct advantages: PDCs realize ligand-receptor-mediated precise targeting, PNs combine gene silencing with favorable biocompatibility, and INs rely on nanozyme activities to maintain redox homeostasis. Despite remarkable preclinical advances, challenges remain in optimizing targeting efficiency, overcoming biological barriers, and ensuring the long-term biosafety of nanomedicines. Future directions will center on stimuli-responsive nanosystems, multimodal therapies, organ-on-a-chip models, and sustainable manufacturing, which are critical for bridging the gap between preclinical research and clinical translation. This review highlights the great potential of nanotechnology in revolutionizing podocyte-targeted therapy and provides a comprehensive preclinical basis for addressing unmet clinical needs in CKD management via interdisciplinary innovation.