Herba Lysimachiae Polysaccharide-Modified Selenium Nanoparticles Alleviate Oxidative Injury in Kidney Stones via TOMM22-Regulated Mitophagy Activation

Pharmacological treatments for kidney stones remain limited, with oxidative stress and injury to renal tubular epithelial cells (RTECs) as key pathological drivers. We prepared a novel Herba Lysimachiae polysaccharide-modified selenium nanoparticle (HLP-SeNPs) formulation that enhances the stability and antioxidant activity of selenium nanoparticles (SeNPs) to alleviate oxalate-induced renal injury. In vivo and in vitro studies showed that HLP-SeNPs possess pronounced anti-oxidative stress capacity, restore mitochondrial membrane potential, alleviate mitochondrial damage, reduce RTEC death, and inhibit renal calcium oxalate (CaOx) crystal deposition. Mechanistically, HLP-SeNPs downregulate TOMM22 (translocase of the outer mitochondrial membrane 22, a core TOM complex subunit) to activate PINK1-Parkin-mediated Mitophagy, thereby effectively limiting oxidative stress-induced injury at its source. These findings indicate that HLP-SeNPs exert substantial renoprotective effects and prevent CaOx stone formation, providing an experimental foundation for mitochondria-targeted nanotherapeutics in kidney stone disease and highlighting the potential of integrating traditional Chinese medicine with nanomaterials.