Reno-protective CT contrast nanoagent targets proximal tubular epithelium for kidney disease imaging and repair in a mouse model
Mingze Xu, Yuming Qi, Yexi Peng, Huixu Lu, Yiqiao Chen, Ziyuan Wang, Yuming Lin, Xingya Jiang, Bujie Du
Abstract
| CT imaging is widely used in clinics for disease diagnosis, but its application in renal function evaluation is limited due to nonspecific distribution and nephrotoxicity of clinical iodinated contrast agents. Herein, we developed an ultrasmall renal-clearable gold nanoparticle-based CT contrast nanoagent (E-Au-Agents) coated with antioxidant L-ergothioneine, enabling reno-targeting and reno-protection for sensitive detection and effective relief of renal dysfunction in female mice. After glomerular filtration, E-Au-Agents specifically recognized OCTN1 transporters on proximal tubular epithelium, followed by clathrin-mediated endocytosis with subsequent tubular reabsorption or re-elimination pathways. This tubular-targeting was markedly enhanced in injured kidneys, allowing rapid CT detection of acute kidney injury, followed by oxidative stress suppression. Remarkably, E-Au-Agents progressively repaired injured kidneys, allowing their eventual clearance through recovered kidneys instead of long-term renal accumulation, a drawback commonly observed in other renal-clearable agents. Collectively, we developed a promising contrast agent for renal CT imaging with dual capabilities of reno-targeting and reno-protection. Application of CT imaging to renal function evaluation is limited due to nonspecific distribution and nephrotoxicity of clinical iodinated contrast agents. Here the authors report the preclinical development of a kidney tubule-targeting and renoprotective CT contrast nanoagent (E-Au-Agent) for detection and repair of kidney injury.