Modulating ferroptosis for the prevention of urinary stone recurrence: An innovative strategy employing Tetrahedral Framework Nucleic acids and Polydatin conjugates

Kidney stone diseases present a serious global health challenge characterized by the development of solid mineral crystals within the renal system. Although conventional surgical treatments exhibit effectiveness, they are constrained by limitations such as recurrence and adverse effects, along with no efficient pharmacotherapeutic options. Our investigation investigated potential of Tetrahedral Framework Nucleic Acids (tFNAs) as a drug carrier, synergistically combining them with Polydatin to formulate an innovative dual therapeutic approach for recurrent kidney stone disease. By the precise delivery offered by tFNAs, Polydatin was effectively transported to the kidney. Experimental results demonstrated the substantial therapeutic impacts in inhibiting kidney stone formation and alleviating tubular injury. Bioinformatic analysis, complemented by both in vitro and in vivo experiments, conclusively elucidated that these effects could be achieved by the regulating ferroptosis. In summary, our study is created a dual-targeted nanoparticle that exhibits multifaceted therapeutic benefits in preventing kidney stone formation, holding potential for future translation into clinical practice.