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Nano Research 2021, 14(3): 762-769 https://doi.org/10.1007/s12274-020-3111-3
Research Article | Issue | Published: 01 March 2021

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

Show Author's Information Yapei Zhang1,2,§,  Jianqin Ye3,§,  Niloufar Hosseini-Nassab6,  Alyssa Flores3,  Irina Kalashnikova1,2,  Sesha Lakshmi Paluri1,2,  Mozhgan Lotfi3,  Nicholas J. Leeper3,4,5,( ),  Bryan Ronain Smith1,2,( )
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
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
Department of Radiology, Stanford University School of Medicine, CA 94305, USA

§ Yapei Zhang and Jianqin Ye contributed equally to this work.

Nicholas J. Leeper and Bryan Ronain Smith contributed equally to this work.

Keywords:
atherosclerosis, macrophages, single-walled carbon nanotubes, phagocytosis, tyrosine phosphatase 1 (SHP-1) inhibitor
Topics:
Antigens Cell signalingControlled drug deliveryMacrophagesNanotubesSingle walled carbon nanotubes (SWCN)
Cite this article:
Zhang Y, Ye J, Hosseini-Nassab N, et al. Macrophage-targeted single walled carbon nanotubes stimulate phagocytosis via pH-dependent drug release. Nano Research, 2021, 14(3): 762-769. https://doi.org/10.1007/s12274-020-3111-3
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Abstract Full text Electronic supplementary material About this article

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.


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Abstract
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Electronic supplementary material
About this article

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

Show Author's information Yapei Zhang1,2,§, Jianqin Ye3,§, Niloufar Hosseini-Nassab6, Alyssa Flores3, Irina Kalashnikova1,2, Sesha Lakshmi Paluri1,2, Mozhgan Lotfi3, Nicholas J. Leeper3,4,5,( ), Bryan Ronain Smith1,2,( )
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
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
Department of Radiology, Stanford University School of Medicine, CA 94305, USA

§ Yapei Zhang and Jianqin Ye contributed equally to this work.

Nicholas J. Leeper and Bryan Ronain Smith contributed equally to this work.

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.

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

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Publication history
Copyright
Acknowledgements

Publication history

Received: 09 March 2020
Revised: 10 September 2020
Accepted: 12 September 2020
Published: 01 March 2021
Issue date: March 2021

Copyright

© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature

Acknowledgements

This study was funded by an AHA Transformational Project grant (No. 18TPA34230113), NIH R01 CA244491, and Falk Catalyst grant. The authors wish to acknowledge Logan Soule for his support in writing the introduction, thank Robert Sinclair, Ai Leen Koh, and Yitian Zeng for their support in TEM characterization, thank Mahsa Gifani for her assistance, and Matthew Bernard and the MSU Flow Cytometry Core for support in Flow cytometry.

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