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Renal Ischaemia Reperfusion Injury: A Mouse Model of Injury and Regeneration
Published on: June 7, 2014
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.
Abstract:
Emerging studies have demonstrated that M1 macrophage polarization and oxidative stress play important roles in calcium oxalate (CaOx) induced kidney injury, which leads to increased crystals deposition. ROS scavenging nanozymes and kidney-targeted nanoparticles for antioxidant drugs delivery have emerged as an arisen methodology for kidney injury therapy. However, cell membrane biomimetic-modified nanozymes as anti-inflammatory drug delivery systems for the treatment of kidney injury is rarely reported. Herein, the ROS responsive red blood cell-membrane-coated resatorvid-loaded cerium oxide nanoparticles (RBCM@CeO2/TAK-242) are constructed to suppress CaOx induced kidney injury and crystals deposition. In vitro, RBCM@CeO2/TAK-242 shows effective internalization by renal tubular epithelial cells, along with demonstrated antioxidative, anti-inflammatory, and macrophage reprogramming effects. Glyoxalate(Gly)-induced renal CaOx crystals mouse model is established, RBCM@CeO2/TAK-242 shows excellent injured kidney targeting and biosafety, and could effectively suppress CaOx induced kidney injury and crystals deposition. RBCM@CeO2/TAK-242 has a dual protective effect by both inhibiting oxidative stress and modulating macrophage polarization in vivo. In addition, RNA seq analysis reveals that RBCM@CeO2/TAK-242 protects against CaOx induced kidney injury via suppressing the TLR4/NF-κB pathway. This study provides an innovative strategy for RBCM@CeO2/TAK-242 as injured kidney targeting and dual protective effects for the treatment of CaOx induced kidney injury and crystals deposition.
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.

