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Improving outcomes in intracerebral hemorrhage through microglia/macrophage-targeted IL-10 delivery with phosphatidylserine liposomes.
Han, Ranran; Lan, Xi; Han, Zheng; Ren, Honglei; Aafreen, Safiya; Wang, Wenshen; Hou, Zhipeng; Zhu, Tianyue; Qian, Andrew; Han, Xiaoning; Koehler, Raymond C; Liu, Guanshu.
Afiliación
  • Han R; Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
  • Lan X; Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
  • Han Z; Russell H. Morgan Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; F.M. Kirby Research Center, Kennedy Krieger Institute, Baltimore, MD, USA; Center for Health Systems Innovation, Oklahoma State University, Stillwater, OK, 74078, USA.
  • Ren H; Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
  • Aafreen S; Russell H. Morgan Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
  • Wang W; Russell H. Morgan Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; F.M. Kirby Research Center, Kennedy Krieger Institute, Baltimore, MD, USA.
  • Hou Z; Russell H. Morgan Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Zhu T; Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
  • Qian A; Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
  • Han X; Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. Electronic address: xhan15@jhmi.edu.
  • Koehler RC; Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. Electronic address: rkoehler@jhmi.edu.
  • Liu G; Russell H. Morgan Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; F.M. Kirby Research Center, Kennedy Krieger Institute, Baltimore, MD, USA. Electronic address: gaunshu@mri.jhu.edu.
Biomaterials ; 301: 122277, 2023 10.
Article en En | MEDLINE | ID: mdl-37597297
Intracerebral hemorrhage (ICH) remains the most lethal type of stroke, and effective clinical therapies that can speed up hematoma resolution after ICH are still lacking. While the beneficial effects of IL-10 on ICH recovery have been demonstrated, the clinical translation of IL-10 requires effective delivery methods by which sufficient IL-10 can be delivered to ICH-affected regions in the brain. Here we report the use of a phosphatidylserine (PS) liposome (PSL)-based nanoparticle system for microglia/macrophage-targeted delivery of IL-10 in ICH. We first prepared IL-10-conjugated PSL (PSL-IL10) and characterized their immunomodulating effects in vitro. Then we evaluated the therapeutic effects, including hematoma absorption, short-term outcomes, and neuroinflammation, of intranasally administered PSL-IL10 (3 µg IL-10 per mouse, 2 h post-ICH) in a collagenase-induced ICH mouse model. We also isolated microglia/macrophages from the mouse brains with ICH to analyze their morphology, phagocytosis ability, and polarization. Our study reveals that, 1) PSL-IL10 treatment resulted in significantly improved outcomes and accelerated hematoma resolution in the acute phase of ICH; 2) PSL-IL10 inhibited glial activation and down-regulated pro-inflammatory cytokine production; 3) PSL-IL10 induced Iba1+ cells with a stronger phagocytosis ability; 4) PSL-IL10 activated STAT3 and upregulated CD36 expression in microglia/macrophage. These findings collectively show that PSL-IL10 is a promising nanotherapeutic for effectively ameliorating ICH.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Interleucina-10 / Microglía Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Biomaterials Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Interleucina-10 / Microglía Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Biomaterials Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos