Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Provincial Key Laboratory of Biotechnology of Shaanxi Province, Northwest University, Xi'an, Shaanxi 710069, China.
School of Science and Chemical Engineering, Ningxia Institute of Science and Technology, Shizuishan, Ningxia 753000, China.
J Mater Chem B. 2024 Mar 6;12(10):2628-2638. doi: 10.1039/d3tb02560h.
Magnetic nanomaterial-mediated magnetic hyperthermia is a localized heating treatment modality that has been applied to treat aggressive cancer in clinics. In addition to being taken up by tumor cells to function in cancer therapy, magnetic nanomaterials can also be internalized by immune cells in the tumor microenvironment, which may contribute to regulating the anti-tumor immune effects. However, there exists little studies on the distribution of magnetic nanomaterials in different types of cells within tumor tissue. Herein, ferrimagnetic vortex-domain iron oxide nanorings (FVIOs) with or without the liver-cancer-targeting peptide SP94 have been successfully synthesized as a model system to investigate the effect of surface modification of FVIOs (with or without SP94) on the distribution of tumor cells and different immune cells in hepatocellular carcinoma (HCC) microenvironment of a mouse. The distribution ratio of FVIO-SP94s in tumor cells was 1.3 times more than that of FVIOs. Immune cells in the liver tumor microenvironment took up fewer FVIO-SP94s than FVIOs. In addition, myeloid cells were found to be much more amenable than lymphoid cells in terms of their ability to phagocytose nanoparticles. Specifically, the distributions of FVIOs/FVIO-SP94s in tumor-associated macrophages, dendritic cells, and myeloid-derived suppressor cells were 13.8%/12%, 3.7%/0.9%, and 6.3%/1.2%, respectively. While the distributions of FVIOs/FVIO-SP94s in T cells, B cells, and natural killer cells were 5.5%/0.7%, 3.0%/0.7%, and 0.4%/0.3%, respectively. The results described in this article enhance our understanding of the distribution of nanomaterials in the tumor microenvironment and provide a strategy for rational design of magnetic hyperthermia agents that can effectively regulate anti-tumor immune effects.
磁性纳米材料介导的磁热疗是一种局部加热治疗方式，已应用于临床治疗侵袭性癌症。除了被肿瘤细胞摄取以在癌症治疗中发挥作用外，磁性纳米材料还可以被肿瘤微环境中的免疫细胞内化，这可能有助于调节抗肿瘤免疫效应。然而，目前关于磁性纳米材料在肿瘤组织内不同类型细胞中的分布的研究较少。在此，我们成功合成了具有或不具有肝癌靶向肽 SP94 的亚铁磁涡旋畴氧化铁纳米环（FVIOs）作为模型系统，以研究 FVIOs（带或不带 SP94）表面修饰对肝癌（HCC）小鼠微环境中肿瘤细胞和不同免疫细胞分布的影响。FVIO-SP94 在肿瘤细胞中的分布比例是 FVIO 的 1.3 倍。肝肿瘤微环境中的免疫细胞摄取的 FVIO-SP94 比 FVIO 少。此外，与淋巴样细胞相比，髓样细胞在吞噬纳米颗粒的能力方面更具优势。具体而言，FVIOs/FVIO-SP94s 在肿瘤相关巨噬细胞、树突状细胞和髓源性抑制细胞中的分布分别为 13.8%/12%、3.7%/0.9%和 6.3%/1.2%。而 FVIOs/FVIO-SP94s 在 T 细胞、B 细胞和自然杀伤细胞中的分布分别为 5.5%/0.7%、3.0%/0.7%和 0.4%/0.3%。本文描述的结果增强了我们对纳米材料在肿瘤微环境中分布的理解，并为合理设计能够有效调节抗肿瘤免疫效应的磁热疗剂提供了策略。
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