4.8 Article

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

Journal

NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -

Publisher

NATURE RESEARCH
DOI: 10.1038/s41467-021-21714-2

Keywords

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Funding

  1. National Key Research and Development Program of China [2016YFA0203600]
  2. National Natural Science Foundation of China [31822019, 32071374, 91859116, 81872878, 81761148029]
  3. One Belt and One Road International Cooperation Project from Key Research and Development Program of Zhejiang Province [2019C04024]
  4. Zhejiang Provincial Natural Science Foundation of China [LGF19C100002, LGF19H310002, LR21H310001]
  5. Fundamental Research Funds for the Central Universities [2019XZZX004-15, 2020FZZX001-05]
  6. CAS Interdisciplinary Innovation Team [JCTD-2020-08]

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Catalytic activity tunable ceria nanoparticles have been reported as potential agents for preventing chemotherapy-induced acute kidney injury without compromising the efficacy of chemotherapeutic agents. This context-dependent reactive oxygen species scavenger shows promise for clinical application in cancer patients.
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. Reactive oxygen species management is a practical strategy that can reduce the risk of chemotherapy-induced acute kidney injury, but at the cost of chemotherapeutic efficacy. Here the authors report catalytic activity tunable ceria nanoparticles as context-dependent reactive oxygen species scavengers, which can prevent chemotherapy-induced acute kidney injury without interfering with chemotherapeutic agents.

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