Nanomaterial-Based Precision Drug Delivery for Advanced Nephrology Therapy: A Systematic Review

Jiayi Feng,1– 4,* Rongrong Zhang,1– 4,* Xu Chen,1– 4 Meng Jia,5 Liang Li,6 Lu Zhang,7 Yi Fu1– 4 1Department of Nephrology, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 2Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 3Key Laboratory for Biotech-Drugs of National Health Commission, Jinan, Shandong, People’s Republic of China; 4Key Laboratory for Genetic Engineering and Synthetic Biology of Shandong Province, Jinan, Shandong, People’s Republic of China; 5Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; 6Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; 7Department of Cardiology, Xiamen Cardiovascular Hospital of Xiamen University, School of Medicine, Fujian Branch of National Clinical Research Center for Cardiovascular Diseases, Xiamen, Fujian, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yi Fu, Department of Nephrology, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, People’s Republic of China, Email [email protected] Lu Zhang, Department of Cardiology, Xiamen Cardiovascular Hospital of Xiamen University, School of Medicine, Fujian Branch of National Clinical Research Center for Cardiovascular Diseases, Xiamen, Fujian, People’s Republic of China, Email [email protected]: Kidney disease represents a serious global health challenge. Current therapeutic strategies often lack the precision to deliver drugs specifically to the kidneys, potentially leading to systemic side effects. Nanomaterials offer a promising alternative, as their size and surface properties can be engineered to facilitate renal accumulation and retention. This systematic review summarizes recent advances in four primary nanomaterial platforms for nephrology therapy, namely lipid nanoparticles, polymeric nanoparticles, inorganic nanoparticles, and exosome delivery system. It focuses on how these rationally designed nanomaterials overcome inherent physiological barriers of the kidney (eg, the glomerular filtration barrier) and how their surface modification with targeting ligands enables response to pathological microenvironments to achieve controlled drug release. Furthermore, the theranostic potential of nanomaterials in kidney disease diagnosis, such as in advanced imaging and disease monitoring, is also discussed. Finally, this review identifies key challenges to the clinical translation of renal nanomedicines, including biosafety, limitations of murine models, insufficient long-term safety, suboptimal targeting accuracy, and scalable manufacturing hurdles, and suggests potential strategies to facilitate their bench-to-bedside translation and improve kidney disease management. In conclusion, this review provides a comprehensive overview of nanomaterial applications in nephrology, clarifying their potential and challenges to lay a foundation for promoting clinical translation and improving kidney disease care.Keywords: nanomaterials, kidney disease, drug delivery systems