A Cationic Metal–Organic Framework to Scavenge Cell-Free DNA for Severe Sepsis Management
| Autor: | Dan Shao, Kam W. Leong, Jie Zhou, Feng Liu, Yanbing Wang, Yongqiang Xiao, Huayu Tian, Yanhui Li, Yiling Zhong, C. H. Quek, Zhiming Hu, Heshi Liu, Xuesi Chen, Shu Sheng |
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| Rok vydání: | 2021 |
| Předmět: |
Bioengineering
Inflammation macromolecular substances 02 engineering and technology Article Nuclear factor kappa b Sepsis chemistry.chemical_compound medicine Humans Polyethyleneimine General Materials Science Metal-Organic Frameworks Severe sepsis Polyethylenimine Mechanical Engineering technology industry and agriculture Cationic polymerization General Chemistry 021001 nanoscience & nanotechnology Condensed Matter Physics medicine.disease chemistry Cell-free fetal DNA Cancer research Nanoparticles medicine.symptom 0210 nano-technology Cell-Free Nucleic Acids DNA |
| Zdroj: | Nano Lett |
| ISSN: | 1530-6992 1530-6984 |
| Popis: | Circulating cell-free DNA (cfDNA) released by damaged cells causes inflammation and has been associated with the progression of sepsis. One proposed strategy to treat sepsis is to scavenge this inflammatory circulating cfDNA. Here, we develop a cfDNA-scavenging nanoparticle (NP) that consists of cationic polyethylenimine (PEI) of different molecular weight grafted to zeolitic imidazolate framework-8 (PEI-g-ZIF) in a simple one-pot process. PEI-g-ZIF NPs fabricated using PEI 1800 and PEI 25k but not PEI 600 suppressed cfDNA-induced TLR activation and subsequent nuclear factor kappa B pathway activity. PEI 1800-g-ZIF NPs showed greater inhibition of cfDNA-associated inflammation and multiple organ injury than naked PEI 1800 (lacking ZIF), and had greater therapeutic efficacy in treating sepsis. These results indicate that PEI-g-ZIF NPs acts as a “nanotrap” that improves upon naked PEI in scavenging circulating cfDNA, reducing inflammation, and reversing the progression of sepsis, thus providing a novel strategy for sepsis treatment. |
| Databáze: | OpenAIRE |
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