WOx Nanosheets Enhance Acute Kidney Injury Therapy Through Geometry-Improved Targeting and Antioxidant Properties

Ultra-small nanoparticles, nanowires, and two-dimensional nanosheets have attracted much attention in acute kidney injury (AKI) treatment. However, the influence of nanostructure geometry on AKI therapy remains unknown. It is important to investigate their biodistribution, clearance, and toxicology to identify the most potential geometry for further nanomedical applications. Herein, three types of oxygen-deficient tungsten oxide (WO_x) nanostructures, nanodots, nanowires, and nanosheets, with attractive reactive oxygen species (ROS) scavenging and computed tomography (CT) imaging properties are bottom-up synthesized, and their in vivo behaviors are systematically studied. The biodistribution results demonstrate that all three WO_x nanostructures can penetrate from the kidney and excrete to the bladder. Interestingly, nanodots can accumulate and be cleared quickly from the kidney, while nanosheets have long retention in vivo. In marked contrast to nanodots and nanosheets, nanowires show high levels in the lung organs with significant cytotoxicity. Therapeutic experiments suggest that nanodots and nanosheets have better therapeutic effects on AKI, but the therapeutic effect of nanowires is not obvious. Furthermore, the nanosheets perform better in alleviating AKI at a lower injection dose than nanodots. This work demonstrates that nanosheets, among various geometries, have particular potential for further AKI treatment because of outstanding performance in CT imaging, renal targeting, long-time retention, and low toxicity. The “structure-function” correlations enable the reasonable design of nanoprobes for AKI theragnostic.