RGD hydrogel-loaded ADSC extracellular vesicles mitigate uranium-induced renal injury via TLR4/NF-κB pathway inhibition

  • J Nanobiotechnology. 2025 Feb 17;23(1):114. doi: 10.1186/s12951-025-03176-6.
Xi Chen  #  1  2 ,  Chun-Mei Dai  #  2  3 ,  Bin Zhang  2  3 ,  Wan-Xin Zhang  2  3 ,  Zheng-Hong Huang  2  4 ,  Jiu-Yi Jiang  2  3 ,  Shi-Qi Hu  1 ,  Jia-Hua Ma  5 ,  Jia-Fu Feng  6  7
Affiliations
  • 1. School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang, Sichuan, 621010, China.
  • 2. NHC Key Laboratory of Nuclear Technology Medical Transformation (MIANYANG CENTRAL HOSPITAL), Affiliated School of Medicine, Mianyang Central Hospital, University of Electronic Science and Technology of China, Mianyang, Sichuan, 621000, China.
  • 3. Department of Medical Laboratory, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China.
  • 4. College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, China.
  • 5. School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang, Sichuan, 621010, China. [email protected].
  • 6. School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang, Sichuan, 621010, China. [email protected].
  • 7. NHC Key Laboratory of Nuclear Technology Medical Transformation (MIANYANG CENTRAL HOSPITAL), Affiliated School of Medicine, Mianyang Central Hospital, University of Electronic Science and Technology of China, Mianyang, Sichuan, 621000, China. [email protected].
  • # Contributed equally.
PMID: 39962465 DOI: 10.1186/s12951-025-03176-6
Abstract

Background: Uranium-induced kidney damage represents a major health concern due to its toxic effects, including mitochondrial dysfunction and inflammation. Mitochondrial DNA (mtDNA)-mediated Pyroptosis is a critical pathway in the pathogenesis of renal injury. The Toll-like Receptor 4 / nuclear factor-kappa B (TLR4/NF-κB) signaling pathway plays a pivotal role in this process. Recent studies have shown that extracellular vesicles derived from adipose-derived stem cells (ADSCs-EVs) possess therapeutic potential due to their anti-inflammatory and regenerative properties. Incorporating ADSCs-EVs into arginine-glycine-aspartate (RGD), hydrogels may enhance their stability and therapeutic efficacy in vivo. This study aims explore the molecular mechanism by which RGD hydrogel-loaded ADSCs-EVs modulate mtDNA-mediated Pyroptosis by suppressing the TLR4/NF-κB signaling pathway to alleviate uranium-induced kidney injury.

Results: Repairing mitochondrial dysfunction was found to mitigate mtDNA leakage, thereby inhibiting renal Pyroptosis. ADSCs-EVs alleviated uranium-induced renal cell damage by suppressing the TLR4/NF-κB signaling pathway. In vivo animal experiments confirmed that RGD hydrogel-loaded ADSCs-EVs enhanced their stability in the body and improved their therapeutic efficacy against kidney injury.

Conclusion: Our findings reveal that RGD hydrogel-loaded ADSCs-EVs effectively inhibit the TLR4/NF-κB signaling pathway, preventing mtDNA-mediated Pyroptosis and alleviating uranium-induced kidney damage. This elucidation provides a novel strategy for utilizing RGD hydrogel-loaded ADSCs-EVs in treating kidney injury.

Keywords
ADSCs-EVs extracellular vesicles; Kidney injury; Mitochondrial DNA; Pyroptosis; RGD hydrogel; TLR4/NF-κB signaling pathway.
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