Ultrasmall self-assembled crystal-modulating amplifier suppresses crystalline nephropathy via dual modulation of mineralization microenvironment and oxidative stress homeostasis

Crystalline nephropathy is a dynamic pathological process characterized by a self-amplifying feedback loop, where crystal-induced epithelial injury drives iterative crystal nucleation, growth, and aggregation, transforming the kidney into a persistent mineralization reactor. Current therapeutic approaches primarily rely on surgical intervention, which fails to disrupt this pathological cycle. The glomerular filtration barrier (10 nm threshold) limits the efficacy of conventional nanomedicines in renal delivery. This study constructs a 5.7 nm metal-polyphenol network, salvianolic acid B-Eu@BSA (SAB-Eu@BSA), via self-assembly methods for editing of the intrarenal crystal microenvironment, aiming to cut off the pathological cycle of renal mineralization. The SAB-Eu@BSA nanoplatform integrates a SAB Eu 3+ coordination core for dual-action: specific adsorption to the high-energy ( 1 ¯ 01) crystal faces of monohydrate calcium oxalate (COM) to inhibit its growth and promote phase transition to less toxic dihydrate phase, and broad-spectrum antioxidant activity to mitigate oxidative stress. The nanoplatform demonstrates enhanced crystal modulation efficacy, significantly reduces crystal-induced renal injury, and improves renal function in vivo. RNA sequencing analysis reveals modulation of key pathways, including oxidative stress, cell adhesion, and apoptosis. This multifunctional nanoplatform, combining crystal inhibition, oxidative stress regulation, and renal clearance, offers a promising therapeutic strategy for crystalline nephropathy.