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Published on: January 24, 2025
Dynamic covalent/coordinated nanonetworks with DNase-mimetic and ROS scavenging properties for acute inflammation
Yan-Qiang Huang1, Xiao Zhang2, Wenlu Li2
1Department of Oncology, Affiliated Hospital of Youjiang Medical University for Nationalities, Key Laboratory of Molecular Pathology in Tumors of Guangxi Higher Education Institutions, Baise, Guangxi 533000, China; Guangxi Technology Innovation Cooperation Base of Prevention and Control Pathogenic Microbes with Drug Resistance, Youjiang Medical University for Nationalities, Baise, Guangxi 533000, China.
A novel nanonetwork effectively clears cell-free DNA and reactive oxygen species, reducing sterile inflammation in acute kidney injury and endometritis models. This approach targets upstream mediators for improved therapeutic outcomes.
Area of Science:
- Biomaterials Science
- Nanomedicine
- Immunology
Background:
- Sterile inflammation, driven by cell-free DNA (cfDNA) and reactive oxygen species (ROS), is central to acute inflammatory diseases.
- Current therapies lack specificity in targeting these upstream inflammatory mediators.
Purpose of the Study:
- To develop a multifunctional nanonetwork (DC²NNW) capable of drug delivery, cfDNA degradation, and ROS scavenging.
- To investigate the therapeutic potential of DC²NNWs in preclinical models of sterile inflammation.
Main Methods:
- Fabrication of a dynamic covalent/coordinated nanonetwork (DC²NNW) via reaction-induced self-assembly and cerium coordination.
- In vitro assessment of cfDNA degradation, ROS scavenging, and drug release capabilities.
- Evaluation of DC²NNW efficacy in murine models of acute kidney injury (AKI) and endometritis, including transcriptomic analysis.
Main Results:
- DC²NNWs demonstrated efficient cfDNA degradation and ROS scavenging, suppressing key inflammatory signaling pathways (TLR9/NF-κB/NLRP3, TLR4/MyD88/JAK).
- In vivo studies showed selective accumulation of DC²NNWs in inflamed tissues, leading to restored organ function, reduced injury, and alleviated oxidative stress.
- Transcriptomic analysis revealed downregulation of pro-inflammatory and neutrophil extracellular trap (NET)-associated genes, with concurrent activation of metabolic repair pathways.
Conclusions:
- The developed multifunctional nanozyme platform offers a targeted, upstream therapeutic strategy for sterile inflammatory diseases.
- DC²NNWs effectively modulate innate immune activation and metabolic dysfunction, showing promise for treating conditions like AKI and endometritis.
