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Background <p>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.</p> Results <p>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.</p> Conclusion <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月6日

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  • Qian Zhao,
  • Di Zhang,
  • Keyan Chen,
  • Feifei Sun,
  • Yixin Chen

摘要

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.