ROS Responsive Cerium Oxide Biomimetic Nanoparticles Alleviates Calcium Oxalate Crystals Induced Kidney Injury via

Yu He1, Ejun Peng1, Xiaozhuo Ba1

  • 1Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Insights

This study developed novel red blood cell-membrane-coated nanoparticles to treat kidney injury caused by calcium oxalate crystals. The nanoparticles effectively reduced oxidative stress and inflammation, offering a dual protective effect for kidney health.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Renal Medicine

Background:

  • Calcium oxalate (CaOx) crystal deposition causes kidney injury, involving M1 macrophage polarization and oxidative stress.
  • Current therapies include ROS scavenging nanozymes and targeted nanoparticles, but biomimetic nanozymes for anti-inflammatory drug delivery in kidney injury are underexplored.

Purpose of the Study:

  • To construct ROS-responsive, red blood cell-membrane-coated cerium oxide nanoparticles loaded with TAK-242 (RBCM@CeO2/TAK-242) for treating CaOx-induced kidney injury.
  • To investigate the in vitro and in vivo therapeutic effects of RBCM@CeO2/TAK-242 on kidney injury and crystal deposition.

Main Methods:

  • Fabrication of red blood cell-membrane-coated cerium oxide nanoparticles loaded with TAK-242.
  • In vitro assessment of cellular uptake, antioxidative, anti-inflammatory, and macrophage reprogramming effects.
  • In vivo evaluation in a glyoxalate-induced CaOx kidney injury mouse model, including targeting, biosafety, and therapeutic efficacy.
  • RNA sequencing to elucidate the underlying molecular pathways.

Main Results:

  • RBCM@CeO2/TAK-242 demonstrated effective internalization by renal cells and exhibited antioxidative, anti-inflammatory, and macrophage modulating properties in vitro.
  • In vivo studies showed excellent kidney targeting, biosafety, and significant suppression of CaOx-induced kidney injury and crystal deposition.
  • The nanoparticles provided dual protection by inhibiting oxidative stress and reprogramming macrophage polarization.
  • RNA sequencing revealed that RBCM@CeO2/TAK-242 functions by suppressing the TLR4/NF-κB signaling pathway.

Conclusions:

  • RBCM@CeO2/TAK-242 nanoparticles offer an innovative therapeutic strategy for CaOx-induced kidney injury.
  • The dual protective effects, targeting injured kidneys, and mechanism via TLR4/NF-κB pathway suppression highlight their potential in treating kidney injury and crystal deposition.