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Nano Research 2023, 16(11): 12855-12863 https://doi.org/10.1007/s12274-023-6266-x
Research Article | Issue | Published: 04 November 2023

Application of mannose-modified fullerene immunomodulator selectively polarizes tumor-associated macrophages potentiating antitumor immunity

Show Author's Information Haoyu Wang1,2,  Lei Li1,2,  Xinran Cao1,2,  Mingming Zhen1,2( ),  Chunru Wang1,2( ),  Chunli Bai1,2
Beijing National Laboratory for Molecular Sciences, Key Laboratory of Molecular Nanostructure and Nanotechnology, CAS Research/Education Center for Excellence in Molecular Sciences, Institution Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China
University of Chinese Academy of Sciences, Beijing 100049, China
Keywords:
cancer immunotherapy, fullerene, macrophage targeting, mannose, tumor-associated macrophage polarization
Topics:
Biomaterials MacrophagesTumors
Cite this article:
Wang H, Li L, Cao X, et al. Application of mannose-modified fullerene immunomodulator selectively polarizes tumor-associated macrophages potentiating antitumor immunity. Nano Research, 2023, 16(11): 12855-12863. https://doi.org/10.1007/s12274-023-6266-x
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Abstract Full text Electronic supplementary material About this article

Polarization of tumor associated macrophages (TAMs) has been a promising therapeutic paradigm for tumor. However, how to achieve precise regulation of TAMs and high efficiency of tumor immunotherapy is still a huge challenge. Here, we report dicarboxy fullerene modified with mannose (DCFM) as an immunomodulator to selectively polarize TAMs and prominently boost anti-tumor immunity. The dicarboxy fullerene molecule was synthesized through the Prato reaction and further covalently bonded with mannose, obtaining the DCFM with well-defined structure. Due to the exist of mannose in DCFM, it could accurately recognize mannose receptor in TAMs. Our cellular experiment results showed that mannose modification could notably promote the uptake of DCFM by the immunosuppressive M2-type macrophages that effectively reprogrammed M2-type macrophages into anti-tumor M1-type macrophages, leading to enhance the phagocytosis of tumor cells by macrophages and inhibiting tumor cells migration. Subsequently, we observed that DCFM could significantly distribute into tumor tissues by in vivo fluorescence imaging. Importantly, DCFM exhibited a superior anti-tumor efficiency in the subcutaneous colorectal tumor model. In addition, it showed that DCFM precisely polarized TAMs into M1-type macrophages and actively increased the infiltration of cytotoxic T lymphocytes (CTLs), inducing profound tumor growth inhibition.


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Abstract
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Electronic supplementary material
About this article

Application of mannose-modified fullerene immunomodulator selectively polarizes tumor-associated macrophages potentiating antitumor immunity

Show Author's information Haoyu Wang1,2, Lei Li1,2, Xinran Cao1,2, Mingming Zhen1,2( ), Chunru Wang1,2( ), Chunli Bai1,2
Beijing National Laboratory for Molecular Sciences, Key Laboratory of Molecular Nanostructure and Nanotechnology, CAS Research/Education Center for Excellence in Molecular Sciences, Institution Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China
University of Chinese Academy of Sciences, Beijing 100049, China

Abstract

Polarization of tumor associated macrophages (TAMs) has been a promising therapeutic paradigm for tumor. However, how to achieve precise regulation of TAMs and high efficiency of tumor immunotherapy is still a huge challenge. Here, we report dicarboxy fullerene modified with mannose (DCFM) as an immunomodulator to selectively polarize TAMs and prominently boost anti-tumor immunity. The dicarboxy fullerene molecule was synthesized through the Prato reaction and further covalently bonded with mannose, obtaining the DCFM with well-defined structure. Due to the exist of mannose in DCFM, it could accurately recognize mannose receptor in TAMs. Our cellular experiment results showed that mannose modification could notably promote the uptake of DCFM by the immunosuppressive M2-type macrophages that effectively reprogrammed M2-type macrophages into anti-tumor M1-type macrophages, leading to enhance the phagocytosis of tumor cells by macrophages and inhibiting tumor cells migration. Subsequently, we observed that DCFM could significantly distribute into tumor tissues by in vivo fluorescence imaging. Importantly, DCFM exhibited a superior anti-tumor efficiency in the subcutaneous colorectal tumor model. In addition, it showed that DCFM precisely polarized TAMs into M1-type macrophages and actively increased the infiltration of cytotoxic T lymphocytes (CTLs), inducing profound tumor growth inhibition.

Keywords: cancer immunotherapy, fullerene, macrophage targeting, mannose, tumor-associated macrophage polarization

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Publication history
Copyright
Acknowledgements

Publication history

Received: 23 August 2023
Revised: 10 October 2023
Accepted: 13 October 2023
Published: 04 November 2023
Issue date: November 2023

Copyright

© Tsinghua University Press 2023

Acknowledgements

Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 92061123). M. M. Z. particularly thanks the Youth Innovation Promotion Association of CAS (No. 2022036).

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