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

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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.

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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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Authors and Affiliations

  1. 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

    Haoyu Wang, Lei Li, Xinran Cao, Mingming Zhen, Chunru Wang & Chunli Bai

  2. University of Chinese Academy of Sciences, Beijing, 100049, China

    Haoyu Wang, Lei Li, Xinran Cao, Mingming Zhen, Chunru Wang & Chunli Bai

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  1. Haoyu Wang
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  2. Lei Li
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  3. Xinran Cao
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  4. Mingming Zhen
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  5. Chunru Wang
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  6. Chunli Bai
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Correspondence to Mingming Zhen or Chunru Wang.

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

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Wang, H., Li, L., Cao, X. et al. Application of mannose-modified fullerene immunomodulator selectively polarizes tumor-associated macrophages potentiating antitumor immunity. Nano Res. 16, 12855–12863 (2023). https://doi.org/10.1007/s12274-023-6266-x

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  • DOI: https://doi.org/10.1007/s12274-023-6266-x

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