Nanoparticle-mediated delivery system alleviates the formation of infection stones by activating TRPV5.

Abstract

Infection stones constitute a small but intractable group of diseases of urinary system. In this study, we explored the potential therapeutic effect of a small activation RNA, ds-320, encapsulated in chitosan (320-chitosan). Western blot analysis verified the downregulation of TRPV5 in patients and rat model of infection stones, as well as the stimulation of ds-320 on TRPV5 expression. MTT assay showed that chitosan-mediated delivery was less cytotoxic to ds-320 compared with liposome delivery. Further a modified invasion assay revealed an inhibitory effect of 320-chitosan on bacterial invasion into normal rat kidney epithelial NRK-52E cells. The establishment of infection stone model was performed by intravesical injection of 1×108 CFU of Proteus mirabilis. In animal experiments, no visible stones were obtained. The number of live bacteria and white blood cells in urine showed no difference among all infected rats at the time of sacrifice. However, we observed a decline in urine calcium and pH, suggesting the effect of acidification. Overall, our study provides evidence for the protective effect of 320-chitosan, for its ability to down-regulate urinary calcium, acidify urine, and inhibit bacteria from invading renal epithelial cells. Thus, it can be served as an important complementary therapy for infection stones.