Cytokine nanosponges suppressing overactive macrophages and dampening systematic cytokine storm for the treatment of hemophagocytic lymphohistiocytosis

Honglan Wang, Huiwen Liu, Jia Li, Chunying Liu, Hui Chen, Junying Li, Chunyan Sun, Tao Guo, Zhiqing Pang, Bo Zhang, Yu Hu

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)
37 Downloads (Pure)

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a highly fatal condition with the positive feedback loop between continued immune cell activation and cytokine storm as the core mechanism to mediate multiple organ dysfunction. Inspired by macrophage membranes harbor the receptors with special high affinity for proinflammation cytokines, lipopolysaccharide (LPS)-stimulated macrophage membrane-coated nanoparticles (LMNP) were developed to show strong sponge ability to both IFN-γ and IL-6 and suppressed overactivation of macrophages by inhibiting JAK/STAT signaling pathway both in vitro and in vivo. Besides, LMNP also efficiently alleviated HLH-related symptoms including cytopenia, hepatosplenomegaly and hepatorenal dysfunction and save the life of mouse models. Furthermore, its sponge effect also worked well for five human HLH samples in vitro. Altogether, it's firstly demonstrated that biocompatible LMNP could dampen HLH with high potential for clinical transformation, which also provided alternative insights for the treatment of other cytokine storm-mediated pathologic conditions such as COVID-19 infection and cytokine releasing syndrome during CAR-T therapy.
Original languageEnglish
Pages (from-to)531-546
Number of pages16
JournalBioactive Materials
Volume21
Early online date20 Sept 2022
DOIs
Publication statusPublished - Mar 2023

Bibliographical note

Copyright the Author(s) 2022. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • Hemophagocytic lymphohistiocytosis
  • Cytokine storm
  • Nanosponge
  • Macrophage activation
  • Macrophage membranes coated nanoparticles
  • Lipopolysaccharide
  • JAK/STAT pathway

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