Multiwalled Carbon Nanotubes Interact with Macrophages and Influence Tumor Progression and Metastasis

Macrophages are one of the most important types of immune effector cells and are closely associated with tumor progression and metastasis. In this work, we investigated the influences of oxidized multiwalled carbon nanotubes (o-MWCNT) on macrophages that are resting in the normal subcutis tissue or in the tumor microenvironment in vivo as well as on the macrophage cell line of RAW 264.7 treated with combination of IL4, IL10 and IL13 in vitro. The o-MWCNT were characterized with SEM, DLS, FTIR, TGA, and UV-vis-NIR spectroscopy, and their effects on the RWA 264.7 cell line and breast cancer tumor-bearing mice were analyzed using the MTS assay, flow cytometry analysis, and histological and immunohistochemical observations. Our experimental results showed that subcutaneously injected o-MWCNT not only induced phagocytosis of the local resident macrophages, but also competitively recruited macrophages from other tissues. These interactions resulted in macrophage reduction and decreased vessel density around the tumor mass, which together inhibited tumor progression and metastasis in the lung. In the cell line model, the o-MWCNT inhibited the ability of the interleukin treated RAW macrophages to promote tumor cell migration as well as decreased their proliferation rate.