A nanotrap improves survival in severe sepsis by attenuating hyperinflammation

Changying Shi, Xiaojing Wang, Lili Wang, Qinghe Meng, Dandan Guo, Li Chen, Matthew Dai, Guirong Wang, Robert Cooney and Juntao Luo ()
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Changying Shi: State University of New York Upstate Medical University
Xiaojing Wang: State University of New York Upstate Medical University
Lili Wang: State University of New York Upstate Medical University
Qinghe Meng: State University of New York Upstate Medical University
Dandan Guo: State University of New York Upstate Medical University
Li Chen: Department of Pathology, Baylor Scott and White Medical Center
Matthew Dai: State University of New York Upstate Medical University
Guirong Wang: State University of New York Upstate Medical University
Robert Cooney: State University of New York Upstate Medical University
Juntao Luo: State University of New York Upstate Medical University

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: Abstract Targeting single mediators has failed to reduce the mortality of sepsis. We developed a telodendrimer (TD) nanotrap (NT) to capture various biomolecules via multivalent, hybrid and synergistic interactions. Here, we report that the immobilization of TD-NTs in size-exclusive hydrogel resins simultaneously adsorbs septic molecules, e.g. lipopolysaccharides (LPS), cytokines and damage- or pathogen-associated molecular patterns (DAMPs/PAMPs) from blood with high efficiency (92–99%). Distinct surface charges displayed on the majority of pro-inflammatory cytokines (negative) and anti-inflammatory cytokines (positive) allow for the selective capture via TD NTs with different charge moieties. The efficacy of NT therapies in murine sepsis is both time-dependent and charge-dependent. The combination of the optimized NT therapy with a moderate antibiotic treatment results in a 100% survival in severe septic mice by controlling both infection and hyperinflammation, whereas survival are only 50–60% with the individual therapies. Cytokine analysis, inflammatory gene activation and tissue histopathology strongly support the survival benefits of treatments.

Date: 2020
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DOI: 10.1038/s41467-020-17153-0

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