Catalytic activity tunable ceria nanoparticles prevent chemotherapy-induced acute kidney injury without interference with chemotherapeutics

Abstract

Acute kidney injury (AKI) is a prevalent and lethal adverse event that severely affects cancer patients receiving chemotherapy. It is correlated with the collateral damage to renal cells caused by reactive oxygen species (ROS). Currently, ROS management is a practical strategy that can reduce the risk of chemotherapy-related AKI, but at the cost of chemotherapeutic efficacy. Herein, we report catalytic activity tunable ceria nanoparticles (CNPs) that can prevent chemotherapy-induced AKI without interference with chemotherapeutic agents. Specifically, in the renal cortex, CNPs exhibit catalytic activity that decomposes hydrogen peroxide, and subsequently regulate the ROS-involved genes by activating the Nrf2/Keap1 signaling pathway. These restore the redox homeostasis for the protection of kidney tubules. Under an acidic tumor microenvironment, CNPs become inert due to the excessive H+ that disrupts the re-exposure of active catalytic sites, allowing a buildup of chemotherapy-mediated ROS generation to kill cancer cells. As ROS-modulating agents, CNPs incorporated with context-dependent catalytic activity, hold a great potential for clinical prevention and treatment of AKI in cancer patients.

Enhanced sunlight photocatalytic activity and biosafety of marine-driven synthesized cerium oxide nanoparticles

“…In recent years, cerium oxide nanoparticles (CeO 2 NPs, nanoceria) have been received momentous interest owing to their inimitable physiochemical properties, biocompatibility, and bioactivities 14 , 15 . They were broadly exploited in various fields such as therapeutics agents in acute kidney injury 16 , catalysis, drug delivery careers, and environmental pollution scavenger 17 . It is found that effective oxidative stress, free-radical scavengers’ role, and enzyme-mimetic catalytic performance of nanoceria mostly due to variation between the Ce 4+ and Ce 3+ cations proportion which on account of oxygen deficiencies in lattice arrangement of their crystal structure.…”

Nanostructured Ceria: Biomolecular Templates and (Bio)applications

“…Ceria NPs can catalyze the dismutation of ·O 2 − into H 2 O 2 at both neutral and acidic pH values, as well as decomposing H 2 O 2 under neutral, but not acidic, pH. Therefore, ceria NPs exerted a general cytoprotection on cells that were challenged by oxidizing chemotherapeutics at a neutral pH, without compromising their anti-tumor activity at an acidic pH, which is a common feature of tumor microenvironments ( Figure 11 ) [ 119 ]. Ceria NPs demonstrated a promising performance to partially revert the cellular mechanisms involved in tumor progression.…”

“…( a ) In the acidic tumor microenvironment, ceria NPs ROS scavenging ability is switched off and does not interfere with oxidizing chemotherapeutics; ( b ) in the neutral pH of the kidneys, ceria NPs scavenge ROS and exert cytoprotection. Reproduced from [ 119 ], under a Creative Commons license .…”

Drug toxicity in the proximal tubule: new models, methods and mechanisms

“…with agents that can block drug transporters, such as cimetidine). Downstream effects of mitochondrial toxicity, including reactive oxide species (ROS) generation, may also be targeted to limit cellular damage [35].…”