Passively-targeted mitochondrial tungsten-based nanodots for efficient acute kidney injury treatment.

ABSTRACT

Acute kidney injury (AKI) can lead to loss of kidney function and a substantial increase in mortality. The burst of reactive oxygen species (ROS) plays a key role in the pathological progression of AKI. Mitochondrial-targeted antioxidant therapy is very promising because mitochondria are the main source of ROS in AKI. Antioxidant nanodrugs with actively targeted mitochondria have achieved encouraging success in many oxidative stress-induced diseases. However, most strategies to actively target mitochondria make the size of nanodrugs too large to pass through the glomerular system to reach the renal tubules, the main damage site of AKI. Here, an ultra-small Tungsten-based nanodots (TWNDs) with strong ROS scavenging can be very effective for treatment of AKI. TWNDs can reach the tubular site after crossing the glomerular barrier, and enter the mitochondria of the renal tubule without resorting to complex active targeting strategies. To our knowledge, this is the first time that ultra-small negatively charged nanodots can be used to passively target mitochondrial therapy for AKI. Through in-depth study of the therapeutic mechanism, such passive mitochondria-targeted TWNDs are highly effective in protecting mitochondria by reducing mitochondrial ROS and increasing mitophagy. In addition, TWNDs can also reduce the infiltration of inflammatory cells. This work provides a new way to passively target mitochondria for AKI, and give inspiration for the treatment of many major diseases closely related to mitochondria, such as myocardial infarction and cerebral infarction.