CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience , National Center for Nanoscience and Technology of China , No. 11, First North Road , Zhongguancun, Beijing 100190 , China.
The College of Life Sciences , Northwest University , Xi'an , Shaanxi 710069 , China.
ACS Nano. 2019 Aug 27;13(8):8811-8825. doi: 10.1021/acsnano.9b01979. Epub 2019 Jul 25.
Cancer metastasis is a serious concern and a major reason for treatment failure. Herein, we have reported the development of an effective and safe nanotherapeutic strategy that can eradicate primary tumors, inhibit metastasizing to lung, and control the metastasis and growth of distant tumors. Briefly, ferrimagnetic vortex-domain iron oxide nanoring (FVIO)-mediated mild magnetic hyperthermia caused calreticulin (CRT) expression on the 4T1 breast cancer cells. The CRT expression transmitted an "eat-me" signal and promoted phagocytic uptake of cancer cells by the immune system to induce an efficient immunogenic cell death, further leading to the macrophage polarization. This mild thermotherapy promoted 88% increase of CD8 cytotoxic T lymphocyte infiltration in distant tumors and triggered immunotherapy by effectively sensitizing tumors to the PD-L1 checkpoint blockade. The percentage of CD8 cytotoxic T lymphocytes can be further increased from 55.4% to 64.5% after combining with PD-L1 blockade. Moreover, the combination treatment also inhibited the immunosuppressive response of the tumor, evidenced by significant down-regulation of myeloid-derived suppressor cells (MDSCs). Our results revealed that the FVIO-mediated mild magnetic hyperthermia can activate the host immune systems and efficiently cooperate with PD-L1 blockade to inhibit the potential metastatic spreading as well as the growth of distant tumors.
癌症转移是一个严重的问题，也是治疗失败的主要原因。在此，我们报告了一种有效且安全的纳米治疗策略的发展，该策略可以根除原发性肿瘤，抑制肺转移，并控制远处肿瘤的转移和生长。简而言之，亚铁磁涡旋域氧化铁纳米环（FVIO）介导的温和磁热疗导致 4T1 乳腺癌细胞表达钙网织蛋白（CRT）。CRT 表达传递了“吃我”信号，并促进了癌细胞被免疫系统吞噬，从而诱导有效的免疫原性细胞死亡，进一步导致巨噬细胞极化。这种温和的热疗促进了远处肿瘤中 CD8 细胞毒性 T 淋巴细胞浸润增加 88%，并通过有效地使肿瘤对 PD-L1 检查点阻断敏感来触发免疫治疗。与 PD-L1 阻断联合使用后，CD8 细胞毒性 T 淋巴细胞的比例可进一步从 55.4%增加到 64.5%。此外，联合治疗还抑制了肿瘤的免疫抑制反应，表现为髓系来源的抑制细胞（MDSCs）的显著下调。我们的结果表明，FVIO 介导的温和磁热疗可以激活宿主免疫系统，并与 PD-L1 阻断有效地合作，抑制潜在的转移性扩散以及远处肿瘤的生长。
