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.