A Cationic Metal-Organic Framework to Scavenge Cell-Free DNA for Severe Sepsis Management.

Mar 11, 2021

Contributor: Feng Liu,Shu Sheng,Dan Shao,Yongqiang Xiao,Yiling Zhong,Jie Zhou,Chai Hoon Quek,Yanbing Wang,Zhiming Hu,Heshi Liu,Yanhui Li,Huayu Tian,Kam W Leong,Xuesi Chen

A Cationic Metal-Organic Framework to Scavenge Cell-Free DNA for Severe Sepsis Management.

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–ZIF) in a simple one-pot process. PEIZIF 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–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 PEIZIF 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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About The Expert

Feng Liu

Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.

Department of Biomedical Engineering, Columbia University, New York City, New York 10027, United States.

University of Chinese Academy of Sciences, Beijing 100049, China.

Shu Sheng

Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.

University of Chinese Academy of Sciences, Beijing 100049, China.

Dan Shao

Institutes for Life Sciences, School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou 510006, China.

Yongqiang Xiao

Department of Biomedical Engineering, Columbia University, New York City, New York 10027, United States.

Yiling Zhong

Department of Biomedical Engineering, Columbia University, New York City, New York 10027, United States.

Jie Zhou

Department of Biomedical Engineering, Columbia University, New York City, New York 10027, United States.

Chai Hoon Quek

Department of Biomedical Engineering, Columbia University, New York City, New York 10027, United States.

Yanbing Wang

Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.

University of Science and Technology of China, Hefei 230026, China.

Zhiming Hu

Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.

Heshi Liu

Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.

Yanhui Li

School of Materials Science and Engineering, Changchun University of Science and Technology, Changchun 130022, China.

Huayu Tian

Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.

University of Chinese Academy of Sciences, Beijing 100049, China.

University of Science and Technology of China, Hefei 230026, China.

Kam W Leong

Department of Biomedical Engineering, Columbia University, New York City, New York 10027, United States.

Xuesi Chen

Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.

University of Chinese Academy of Sciences, Beijing 100049, China.

University of Science and Technology of China, Hefei 230026, China.

References

PubMed