Polarization and function of tumor-associated macrophages mediate graphene oxide-induced photothermal cancer therapy.

Polarization status of tumor-associated macrophages (TAMs) plays an essential role in tumor growth and invasion. However, emerging treatment like photothermal therapy (PTT), photodynamic therapy (PDT) paid little attention on TAMs. In recent years, photothermal therapy (PTT) has gained immense attention in the anti-tumor strategy field while the effect of PTT on macrophage polarization in a tumor microenvironment has rarely been reported. Here, we used graphene oxide (GO) combined with polyethylene glycol (PEG) as the photothermal material to induce heating effect in macrophages to define its anti-tumor effect in vitro and in vivo. Firstly, we treated the macrophage cell line RAW264.7 with near infrared (NIR) light irradiation and detected their polarization status by flow cytometric and mRNA expression analysis. Following this, we analyzed the migration and invasion ability of an osteosarcoma HOS cell line cultured in a conditioned medium (CM) that contains cytokine generated by macrophages with or without NIR treatment. Finally, we investigated the in vivo effects of NIR-induced macrophage polarization on osteosarcoma growth and invasion. GO-PEG (GP) showed great photothermal effect, thermal stability, and biocompatibility in vitro and in vivo. Photothermal materials can alleviate interleukin-4-induced M2 polarization of macrophages and modulate their anti-tumor capability. Thus, the migration and invasion capabilities of HOS cells were weakened, leading to an anti-tumor effect in a mouse subcutaneous tumor model. In conclusion, our study identified PTT treatment as an approach for preventing osteosarcoma invasion by inhibition of M2 polarization.