Development of Serine Modification-based Kidney-targeted Drug Delivery System

Kidney-targeted drug delivery is vital in treating kidney diseases by improving therapeutic efficacy and safety. However, targeting drugs to the kidney is challenging, as drug nano-carriers are usually trapped by the reticuloendothelial system in the liver and spleen. Recently, we reported that serine-modified polyamidoamine (Ser-PAMAM) dendrimer functions as a highly potent kidney-targeting drug carrier. Further, we demonstrated that Ser-PAMAM predominantly accumulated in the kidney, especially in proximal tubules, a pattern associated with the pathogenesis of chronic kidney diseases and renal carcinoma cells. Furthermore, captopril was successfully targeted to the kidney using Ser-PAMAM, and cysteine- or S-nitrosothiol (source of nitric oxide)-loaded Ser-PAMAM effectively suppressed the occurrence of renal injury following renal ischemia/reperfusion. In this review, we summarized recent challenges in developing a kidney-targeted drug delivery system and discussed the utility of our serine modification-based improvements to this system for the efficient treatment of kidney diseasse.