FeO 纳米颗粒调节肿瘤相关巨噬细胞的极化，与光热疗法和免疫疗法（PD-1/PD-L1 抑制剂）协同增效，增强抗肿瘤治疗。

INTRODUCTION: Traditional surgical resection, radiotherapy, and chemotherapy have been the treatment options for patients with head and neck squamous cell carcinoma (HNSCC) over the past few decades. Nevertheless, the five-year survival rate for patients has remained essentially unchanged, and research into treatments has been relatively stagnant. The combined application of photothermal therapy (PTT) and immunotherapy for treating HNSCC has considerable potential. METHODS: Live-dead cell staining and CCK-8 assays proved that FeO nanoparticles are biocompatible in vitro. In vitro, cellular experiments utilized flow cytometry and immunofluorescence staining to verify the effect of FeO nanoparticles on the polarisation of tumor-associated macrophages. In vivo, animal experiments were conducted to assess the inhibitory effect of FeO nanoparticles on tumor proliferation under the photothermal effect in conjunction with BMS-1. Tumour tissue sections were stained to observe the effects of apoptosis and the inhibition of tumor cell proliferation. The histological damage to animal organs was analyzed by hematoxylin and eosin (H&E) staining. RESULTS: The stable photothermal properties of FeO nanoparticles were validated by in vitro cellular and in vivo animal experiments. FeO photothermal action not only directly triggered immunogenic cell death (ICD) and enhanced the immunogenicity of the tumor microenvironment but also regulated the expression of tumor-associated macrophages (TAMs), up-regulating CD86 and down-regulating CD206 to inhibit tumor growth. The PD-1/PD-L1 inhibitor promoted tumor suppression, and reduced tumor recurrence and metastasis. In vivo studies demonstrated that the photothermal action exhibited a synergistic effect when combined with immunotherapy, resulting in significant suppression of primary tumors and an extension of survival. CONCLUSION: In this study, we applied FeO photothermolysis in a biomedical context, combining photothermolysis with immunotherapy, exploring a novel pathway for treating HNSCC and providing a new strategy for effectively treating HNSCC.

简介：在过去的几十年中，传统的手术切除、放疗和化疗一直是头颈部鳞状细胞癌（HNSCC）患者的治疗选择。然而，患者的五年生存率基本保持不变，且治疗研究相对停滞不前。光热疗法（PTT）和免疫疗法联合应用于治疗 HNSCC 具有很大的潜力。

方法：活/死细胞染色和 CCK-8 测定证明了 FeO 纳米颗粒在体外具有生物相容性。在体外，细胞实验利用流式细胞术和免疫荧光染色验证了 FeO 纳米颗粒对肿瘤相关巨噬细胞极化的影响。在体内，动物实验评估了在光热效应结合 BMS-1 作用下 FeO 纳米颗粒对肿瘤增殖的抑制作用。肿瘤组织切片染色观察凋亡和肿瘤细胞增殖抑制的影响。通过苏木精和伊红（H&E）染色分析动物器官的组织学损伤。

结果：通过体外细胞实验和体内动物实验验证了 FeO 纳米颗粒的稳定光热性能。FeO 光热作用不仅直接引发免疫原性细胞死亡（ICD）和增强肿瘤微环境的免疫原性，还调节肿瘤相关巨噬细胞（TAMs）的表达，上调 CD86 并下调 CD206 以抑制肿瘤生长。PD-1/PD-L1 抑制剂促进肿瘤抑制，减少肿瘤复发和转移。体内研究表明，光热作用与免疫疗法联合具有协同作用，显著抑制原发性肿瘤并延长生存时间。

结论：在这项研究中，我们将 FeO 光热解应用于生物医学领域，将光热解与免疫疗法相结合，探索了治疗 HNSCC 的新途径，为有效治疗 HNSCC 提供了新策略。