Simultaneous Elimination of Reactive Oxygen Species and Activation of Nrf2 by Ultrasmall Nanoparticles to Relieve Acute Kidney Injury

Abstract

Excess reactive oxygen species (ROS) can induce serious acute kidney injury (AKI) to result in numerous deaths annually in clinical practice. Elimination of excess ROS by advanced nanotechnology is a very promising AKI therapy. In this Article, we report that PVP-stabilized and quercetin-functionalized ultrasmall Cu2–x Se nanoparticles (abbreviated as CSPQ NPs) can efficiently scavenge ROS and increase the expression of intracellular antioxidative enzymes by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) protein, which drastically alleviates the cellular oxidative stress. Our ultrasmall nanoparticles exhibit excellent biocompatibility. They can be rapidly accumulated into the injured kidney to simultaneously eliminate ROS and activate Nrf2 to improve the renal function. This work demonstrates the great potential of simultaneous elimination of ROS and activation of intracellular Nrf2 in treatment of AKI. It also highlights the potential of CSPQ NPs in protection and prevention of AKI.

Ultrasmall Nanoparticles Regulate Immune Microenvironment by Activating IL‐33/ST2 to Alleviate Renal Ischemia‐Reperfusion Injury

“…However, the harm caused was lessened when the AKI mice were treated with CSPB NPs. Tubular damage scores were calculated by the previously reported method, [54] which shows that the overall kidney tissue damage was reduced after the AKI mice were treated with CSPB NPs (Figure 4d).…”

A bimetallic nanozyme coordinated with quercetin for efficient radical scavenging and treatment of acute kidney injury

“…41–43 In their study, Bao et al synthesized and analyzed polyvinylpyrrolidone (PVP)-stabilized and quercetin-functionalized ultrasmall Cu 2− x Se nanoparticles that demonstrated the ability to mitigate glycerol-induced AKI and enhance renal function by effectively scavenging ROS and upregulating the Nrf2 protein. 44 In addition, Casanova et al reported the development of a micellar formulation of quercetin, which exhibited enhanced bioavailability and water solubility compared to free quercetin, and demonstrated promising therapeutic efficacy in the treatment of cisplatin-induced AKI. 45 However, the treatment of AKI through the development of new quercetin-functionalized nanozymes that possess antioxidant and anti-inflammatory properties still holds promising potential.…”

Sulfated Laminarin Polysaccharides Reduce the Adhesion of Nano-COM Crystals to Renal Epithelial Cells by Inhibiting Oxidative and Endoplasmic Reticulum Stress

“…When the production of ROS surpasses the cellular antioxidant defense mechanisms, it triggers the oxidation of various cellular components, such as DNA, lipids, and proteins. This oxidation can damage the cellular matrix, resulting in oxidative stress, ultimately leading to cellular damage [ 2 , 3 ]. Research indicates a close correlation between the impairment of renal tubular epithelial cells and the early pathological changes associated with kidney stone formation [ 4 ].…”