Emerging applications of nanotechnology in the treatment of acute kidney injury.

Acute kidney injury (AKI) is a life-threatening condition with high mortality rates and limited treatment options. Recent advances in nanotechnology offer transformative potential for AKI therapy by enabling targeted drug delivery, enhancing therapeutic bioavailability, and minimizing off-target effects. This review highlights the emerging applications of nanomedicine in AKI, focusing on 1) passive and active targeting strategies to optimize renal nanoparticle (NP) accumulation, including size-, charge-, and ligand-dependent approaches, 2) mechanism-based therapeutic innovations, such as antioxidant, anti-inflammatory, anti-apoptotic, and anti-ferroptotic nanotherapeutics, and 3) critical challenges in biocompatibility, biodistribution, scalability, and regulatory translation. A systematic literature search was conducted in PubMed and Google Scholar, focusing on studies published between 2015 and 2025. While preclinical studies demonstrate remarkable efficacy in mitigating AKI pathogenesis, significant hurdles still exist, including risks of NP toxicity, limited and variable filtration across the glomerular barrier, manufacturing reproducibility, and lack of standardized regulatory frameworks. We highlight cutting-edge solutions, such as dynamic targeting ligands, green synthesis methods, and organ-on-a-chip models, to bridge these gaps. By addressing these challenges, nanotechnology could revolutionize AKI management, offering precision therapies tailored to the molecular and cellular underpinnings of renal injury.