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Multiwalled Carbon Nanotubes Prevent Tumor Metastasis Through Switching M2-Polarized Macrophages to M1 via TLR4

Lianlian Wu, Hongling Tang, Hao Zheng

    Journal of Biomedical Nanotechnology
    |November 28, 2018
    PubMed

    Insights

    Carboxylated multiwalled carbon nanotubes (MWCNTs-COOH) reduce cancer metastasis by reprogramming tumor-associated macrophages (TAMs). MWCNTs-COOH shift macrophages to an anti-tumor M1 state, inhibiting tumor spread.

    Area of Science:

    • Nanomedicine
    • Immunology
    • Oncology

    Background:

    • Tumor-associated macrophages (TAMs) play a critical role in promoting cancer metastasis.
    • Targeting TAMs presents a promising therapeutic avenue for cancer treatment.

    Purpose of the Study:

    • To investigate the potential of carboxylated multiwalled carbon nanotubes (MWCNTs-COOH) in preventing tumor metastasis.
    • To elucidate the mechanism by which MWCNTs-COOH regulate macrophage polarization.

    Main Methods:

    • Administration of MWCNTs-COOH to Lewis lung carcinoma and B16F10 melanoma mouse models.
    • Assessment of metastatic burden, macrophage polarization markers (M1/M2), cytokine profiles, and TLR4/NF-κB signaling.
    • In vitro studies using macrophages treated with MWCNTs-COOH and LLC cells.
    • Evaluation of the effects of a TLR4 inhibitor (TAK-242) on MWCNTs-COOH activity.

    Main Results:

    • MWCNTs-COOH significantly reduced lung metastatic burden in mice.
    • MWCNTs-COOH promoted M1 macrophage polarization (increased iNOS, CXCR10; decreased CD206, Arg-1) and Th1 cytokines, while suppressing M2 markers and Th2 cytokines.
    • Macrophage depletion reversed the anti-metastatic effects, confirming their crucial role.
    • In vitro, MWCNTs-COOH induced M1 polarization via TLR4/NF-κB signaling, inhibiting cancer cell migration and invasion.
    • TLR4 inhibition abrogated MWCNTs-COOH-mediated effects on macrophage polarization.

    Conclusions:

    • MWCNTs-COOH effectively prevent tumor metastasis by reprogramming M2-polarized TAMs to an M1 phenotype.
    • The mechanism involves the activation of the TLR4/NF-κB signaling pathway.
    • MWCNTs-COOH represent a potential nanotherapeutic strategy for combating cancer metastasis by targeting TAMs.

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