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.

肿瘤相关巨噬细胞（TAM）的极化状态在肿瘤的生长和侵袭中起着至关重要的作用。然而，诸如光热疗法（PTT），光动力疗法（PDT）等新兴疗法对TAM的关注很少。近年来，光热疗法（PTT）在抗肿瘤策略领域引起了极大的关注，而在肿瘤微环境中，PTT对巨噬细胞极化的影响却鲜有报道。在这里，我们使用氧化石墨烯（GO）与聚乙二醇（PEG）结合作为光热材料来诱导巨噬细胞的加热作用，以定义其在体内和体外的抗肿瘤作用。首先，我们用近红外（NIR）光处理巨噬细胞系RAW264.7，并通过流式细胞仪和mRNA表达分析检测其极化状态。按照此，我们分析了在条件培养基（CM）中培养的骨肉瘤HOS细胞系的迁移和侵袭能力，该培养基含有巨噬细胞经或不经过NIR处理而产生的细胞因子。最后，我们研究了NIR诱导的巨噬细胞极化对骨肉瘤生长和侵袭的体内影响。GO-PEG（GP）在体外和体内均表现出出色的光热效应，热稳定性和生物相容性。光热材料可以减轻白细胞介素4诱导的巨噬细胞M2极化并调节其抗肿瘤能力。因此，HOS细胞的迁移和侵袭能力被削弱，导致在小鼠皮下肿瘤模型中的抗肿瘤作用。

总之，我们的研究确定PTT治疗是通过抑制M2极化来预防骨肉瘤浸润的方法。