Novel multifunctional targeted nanozyme as an ultrasound contrast agent for real-time monitoring and treatment of congenital hydronephrosis renal fibrosis.

BACKGROUND: Congenital Hydronephrosis (CH) is a common pediatric disorder that often leads to renal fibrosis (RF), significantly impairing kidney function. Oxidative stress (OS) plays a central role in the pathogenesis of RF. Current treatments lack effective monitoring and targeted therapies for CH, thus highlighting the need for innovative diagnostic and therapeutic approaches. This study explores a novel multifunctional nanozyme, pH-responsive PEG-SH and imidazole-modified gold nanoparticles (PMIZ-AuNPs), for both real-time ultrasound monitoring and treatment of CH-induced RF. RESULTS: We designed a pH-responsive nanozyme, consisting of PEG-SH and PMIZ-AuNPs. This nanozyme exhibits enhanced ultrasound imaging properties and dual catalytic activities, including superoxide dismutase (SOD) and catalase (CAT), under acidic conditions. In a unilateral ureteral obstruction (UUO) mouse model, PMIZ-AuNPs accumulated at injury sites, enhancing ultrasound signal intensity and improving RF. Protein sequencing and bioinformatics analysis identified C9 as a critical gene involved in RF. Further experiments showed that PMIZ-AuNPs reduced C9 expression by inhibiting OS and modulated the TGF-β signaling pathway, leading to significant attenuation of RF in both in vitro and in vivo models. CONCLUSION: PMIZ-AuNPs demonstrate significant potential as a multifunctional tool for the diagnosis and treatment of CH-induced RF. By targeting oxidative stress and modulating C9 expression, PMIZ-AuNPs improve renal function and offer a promising strategy for the clinical management of CH.