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

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

机构地区：[1]Institute of Hematology,Union Hospital,Tongji Medical College,Huazhong University of Science&Technology,Wuhan,Hubei,430022,PR China [2]School of Pharmacy,Fudan University,Key Laboratory of Smart Drug Delivery,Ministry of Education,826 Zhangheng Road,Shanghai,201203,PR China [3]Department of Biomedical Sciences,Faculty of Medicine,Health and Human Sciences,Macquarie University,Sydney NSW,2109,Australia [4]Department of Infectious Diseases,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,430022,PR China

出　　处：《Bioactive Materials》2023年第3期531-546,共16页生物活性材料（英文）

基　　金：National Natural Science Foundation of China(82070228,81773283);National Key R&D Program of China(No.2019YFC1316204)。

摘　　要：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 proin-flammation cytokines,lipopolysaccharide(LPS)-stimulated macrophage membrane-coated nanoparticles(LMNP)were developed to show strong sponge ability to both IFN-γand 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.

关 键 词：Hemophagocytic lymphohistiocytosis Cytokine storm Nanosponge Macrophage activation Macrophage membranes coated nanoparticles LIPOPOLYSACCHARIDE JAK/STAT pathway 

分 类 号：R318[医药卫生—生物医学工程]