Advances in the Targeted Drug Delivery System for Renal Fibrosis

Renal fibrosis represents the ultimate outcome of almost all chronic kidney diseases (CKD), and is the primary cause of end-stage renal disease, making it a serious global health burden. Despite numerous preclinical drugs demonstrating potential in the treatment of renal fibrosis, the majority fail to fulfill the stringent criteria for clinical applications. Key hurdles in renal fibrosis therapy not only involve intricate signaling networks and fibrosis-perpetuating microenvironments, complex renal structures, and pathological barriers, but also restrict drug delivery to lesions. Therefore, recent delivery system focused on co-delivering multiple drugs via nanoplatforms and functionalized with targeting ligands. These systems enable precise drug delivery to key effector cells in fibrosis (eg, myofibroblasts and tubular epithelial cells), thereby achieving targeted and highly effective therapy. This review summarizes the signaling pathways of renal fibrosis using the concept of the fibrosis niche and critically evaluates both drug delivery barriers and emerging targeted drug delivery system (TDDS). Furthermore, the potential challenges and future directions of TDDS for reversing renal fibrosis are discussed with the aim of providing guidance for the development of new therapeutic strategies.