UCL Cancer Institute, University College London (UCL), Paul O'Gorman Building, 72 Huntley Street, London, WC1E 6DD, UK.
UCL Healthcare Biomagnetics Laboratory, 21 Albermarle Street, London, W1S 4BS, UK.
Small. 2021 Apr;17(14):e2005241. doi: 10.1002/smll.202005241. Epub 2021 Mar 18.
Magnetic hyperthermia (MH) harnesses the heat-releasing properties of superparamagnetic iron oxide nanoparticles (SPIONs) and has potential to stimulate immune activation in the tumor microenvironment whilst sparing surrounding normal tissues. To assess feasibility of localized MH in vivo, SPIONs are injected intratumorally and their fate tracked by Zirconium-89-positron emission tomography, histological analysis, and electron microscopy. Experiments show that an average of 49% (21-87%, n = 9) of SPIONs are retained within the tumor or immediately surrounding tissue. In situ heating is subsequently generated by exposure to an externally applied alternating magnetic field and monitored by thermal imaging. Tissue response to hyperthermia, measured by immunohistochemical image analysis, reveals specific and localized heat-shock protein expression following treatment. Tumor growth inhibition is also observed. To evaluate the potential effects of MH on the immune landscape, flow cytometry is used to characterize immune cells from excised tumors and draining lymph nodes. Results show an influx of activated cytotoxic T cells, alongside an increase in proliferating regulatory T cells, following treatment. Complementary changes are found in draining lymph nodes. In conclusion, results indicate that biologically reactive MH is achievable in vivo and can generate localized changes consistent with an anti-tumor immune response.
磁热疗（MH）利用超顺磁氧化铁纳米粒子（SPIONs）的发热特性，有潜力在肿瘤微环境中刺激免疫激活，同时保护周围正常组织。为了评估体内局部 MH 的可行性，将 SPIONs 瘤内注射，并通过锆-89 正电子发射断层扫描、组织学分析和电子显微镜跟踪其命运。实验表明，平均有 49%（21-87%，n=9）的 SPIONs 保留在肿瘤或紧邻的组织中。然后通过暴露于外部施加的交变磁场产生原位加热，并通过热成像进行监测。通过免疫组织化学图像分析测量热疗后的组织反应，发现治疗后会出现特异性和局部性热休克蛋白表达。还观察到肿瘤生长抑制。为了评估 MH 对免疫图谱的潜在影响，使用流式细胞术对切除的肿瘤和引流淋巴结中的免疫细胞进行特征分析。结果表明，治疗后会有激活的细胞毒性 T 细胞涌入，同时增殖的调节性 T 细胞也会增加。在引流淋巴结中也发现了补充性变化。总之，结果表明，体内可实现具有生物反应性的 MH，并能产生与抗肿瘤免疫反应一致的局部变化。
