Ultrasound Captured-Nanomachine for Restarting Healthy Renal Function.

Acute kidney injury (AKI) was a common clinical emergency with serious complications, and its treatment remains challenging. Here, we designed a biocompatible, ultrasound-captured nanomachine (NTMCH) that proactively delivered carbon monoxide (CO) under ultrasound. This system achieved kidney protection and enhanced renal clearance in a mouse model of AKI. The nanomachine was fabricated by coating niobium on one side of amine-functionalized mesoporous TiO2, followed by dimanganese decacarbonyl (Mn2(CO)10) loading and hyaluronic acid modification. Asymmetric CO release both propelled the nanomachine and acted as a therapeutic gas. At the kidney injury site, ultrasound triggers CO release, which stimulates ROS generation from mesoporous titanium dioxide (MTD), cascading Mn2(CO)10 activation. This enhanced CO diffusion and renal clearance in synergy with Nb. This ultrasound-responsive nanomachine offered outstanding potential for kidney protection via CD44 regulation, with findings that could advance future clinical development.