Journal
NANO LETTERS
Volume 21, Issue 6, Pages 2461-2469Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.0c04759
Keywords
sepsis; cell-free DNA; metal-organic framework; polyethylenimine; nanotrap
Categories
Funding
- National Natural Science Foundation of China [51925305, 51873208, 51520105004, 51833010]
- National Science and Technology Major Projects for Major New Drugs Innovation and Development [2018ZX09711003012]
- Jilin Province Science and Technology Development Program [20180414027GH]
- NIH [AR073935]
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A novel cfDNA-scavenging nanoparticle (NP) has been developed as a potential treatment for sepsis. This nanoparticle showed superior efficacy in scavenging circulating cfDNA, reducing inflammation, and reversing the progression of sepsis compared to naked PEI.
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 cIDNA-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.
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