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Nano Research

Article Title

Macrophage-targeted single walled carbon nanotubes stimulate phagocytosis via pH-dependent drug release

Authors

Yapei Zhang, Department of Biomedical Engineering, Michigan State University, East Lansing, MI 48824, USA;Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI 48824, USA
Jianqin Ye, Department of Surgery, Division of Vascular Surgery, Stanford University School of Medicine, CA 94305, USA
Niloufar Hosseini-Nassab, Department of Radiology, Stanford University School of Medicine, CA 94305, USA
Alyssa Flores, Department of Surgery, Division of Vascular Surgery, Stanford University School of Medicine, CA 94305, USA
Irina Kalashnikova, Department of Biomedical Engineering, Michigan State University, East Lansing, MI 48824, USA;Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI 48824, USA
Sesha Lakshmi Paluri, Department of Biomedical Engineering, Michigan State University, East Lansing, MI 48824, USA;Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI 48824, USA
Mozhgan Lotfi, Department of Surgery, Division of Vascular Surgery, Stanford University School of Medicine, CA 94305, USA
Nicholas J. Leeper, Department of Surgery, Division of Vascular Surgery, Stanford University School of Medicine, CA 94305, USA;Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, CA 94305, USA;Stanford Cardiovascular Institute, Stanford, CA 94305, USA
Bryan Ronain Smith, Department of Biomedical Engineering, Michigan State University, East Lansing, MI 48824, USA;Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI 48824, USA

Keywords

macrophages, phagocytosis, single-walled carbon nanotubes, tyrosine phosphatase 1 (SHP-1) inhibitor, atherosclerosis

Abstract

Atherosclerotic cardiovascular disease is the leading cause of mortality in the world. A driving feature of atherosclerotic plaque formation is dysfunctional efferocytosis. Because the "don’t eat me" molecule CD47 is upregulated in atherosclerotic plaque cores, CD47-blocking strategies can stimulate the efferocytic clearance of apoptotic cells and thereby help prevent the progression of plaque buildup. However, these therapies are generally costly and, in clinical and murine trials, they have resulted in side effects including anemia and reticulocytosis. Here, we developed and characterized an intracellular phagocytosis-stimulating treatment in the CD47-SIRPα pathway. We loaded a novel monocyte/macrophage-selective nanoparticle carrier system with a small molecule enzymatic inhibitor that is released in a pH-dependent manner to stimulate macrophage efferocytosis of apoptotic cell debris via the CD47-SIRPα signaling pathway. We demonstrated that single-walled carbon nanotubes (SWNTs) can selectively deliver tyrosine phosphatase inhibitor 1 (TPI) intracellularly to macrophages, which potently stimulates efferocytosis, and chemically characterized the nanocarrier. Thus, SWNT-delivered TPI can stimulate macrophage efferocytosis, with the potential to reduce or prevent atherosclerotic disease.

Publisher

Tsinghua University Press

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