ROS-responsive curcumin-encapsulated nanoparticles for AKI therapy via promoting lipid degradation in renal tubules.

Lipid accumulation is a factor contributing to the pathogenesis of acute kidney injury (AKI), yet there are currently no approved pharmacotherapies aside from adjuvant therapy. A developed reactive oxygen species (ROS)-responsive drug delivery system (NPSBG@Cur) was developed to deliver the autophagy activator curcumin (Cur) in order to alleviate AKI by activating autophagy and promoting lipid droplet degradation. The nanoparticles were shown to be ROS-responsive in the H2O2 medium and demonstrate ROS-responsive uptake in palmitate (PA)-induced oxidative stress-damaged cells. NPSBG@Cur was found to effectively inhibit lipid accumulation by autophagosome transport in kidney tubular cells. Additionally, in a mouse AKI model, NPSBG@Cur was observed to significantly ameliorate renal damage by activating autophagy flux and improving lipid transport. These results suggest that the ROS-responsive drug delivery system augmented the therapeutic effect of Cur on AKI by improving lipid metabolism through autophagy activation. Therefore, targeting lipid metabolism with NPSBG@Cur may be a promising AKI treatment strategy.

Dual-Responsive Curcumin-Loaded Nanoparticles for the Treatment of Cisplatin-Induced Acute Kidney Injury.

Acute kidney injury (AKI) has been a global public health concern leading to high patient morbidity and mortality in the world. Nanotechnology-mediated antioxidative therapy has facilitated the treatment of AKI. Herein, a hierarchical curcumin-loaded nanodrug delivery system (NPS@Cur) was fabricated for antioxidant therapy to ameliorate AKI. The nanoplatform could respond to subacidic and reactive oxygen species (ROS) microenvironments. The subacidic microenvironment led to a smaller size (from 140.9 to 99.36 nm) and positive charge (from -4.9 to 12.6 mV), contributing to the high accumulation of nanoparticles. An excessive ROS microenvironment led to nanoparticle degradation and drug release. In vitro assays showed that NPS@Cur could scavenge excessive ROS and relieve oxidative stress in H2O2-induced HK-2 cells through reduced apoptosis, activated autophagy, and decreased endoplasmic reticulum stress. Results from cisplatin-induced AKI models revealed that NPS@Cur could effectively alleviate mitochondria injury and protect kidneys via antioxidative protection, activated autophagy, decreased endoplasmic reticulum stress, and reduced apoptosis. NPS@Cur showed excellent biocompatibility and low toxicity to primary tissues in mice. These results revealed that NPS@Cur may be a potential therapeutic strategy for efficiently treating cisplatin or other cause-induced AKI.