Breaking the fibrotic code: Nanotechnology-driven advances in renal fibrosis therapy

Renal fibrosis, a hallmark of chronic kidney disease progression, arises from complex pathogenic mechanisms involving inflammatory activation, myofibroblast proliferation, and excessive extracellular matrix deposition. Current treatment is limited by poor bioavailability and off-target effects. This review elaborates on how nanotechnology can overcome these obstacles by delivering targeted drugs to fibrotic kidneys. The pathogenesis of renal fibrosis was systematically analyzed, emphasizing the heterogeneity and plasticity of myofibroblast origin and activation. Then the mechanisms of nanoparticle transport in the kidneys, particularly the impact of the fibrotic environment on nanoparticle transport were focused on. The design principles of active and passive targeting of the kidneys by nano-delivery systems in the context of fibrosis are also discussed. Additionally, emerging renal-targeted nanocarriers are summarized, and therapeutic nanomedicines for fibrosis relief are rigorously evaluated. Despite the progress made, challenges remain in the design optimization of nanocarriers, the intelligence of nanomaterials, and the clinical translation of nanomedicines. Future research directions should focus on AI-assisted nanocarrier design, innovation in intelligent nanomaterials, and the application of humanized models. In conclusion, this review highlights the potential of nanomedicine in reshaping the treatment of renal fibrosis and provides practical innovative insights for promoting in-depth and translational research in the future.