Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Medicine , Northwest University , 229 Taibai North Road , Xi'an 710069 , China.
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.
ACS Nano. 2020 Feb 25;14(2):1936-1950. doi: 10.1021/acsnano.9b08320. Epub 2020 Jan 24.
In this study, a magnetothermodynamic (MTD) therapy is introduced as an efficient systemic cancer treatment, by combining the magnetothermal effect and the reactive oxygen species (ROS)-related immunologic effect, in order to overcome the obstacle of limited therapeutic efficacy in current magnetothermal therapy (MTT). This approach was achieved by the development of an elaborate ferrimagnetic vortex-domain iron oxide nanoring and graphene oxide (FVIOs-GO) hybrid nanoparticle as the efficient MTD agent. Such a FVIOs-GO nanoplatform was shown to have high thermal conversion efficiency, and it was further proved to generate a significantly amplified ROS level under an alternating magnetic field (AMF). Both and results revealed that amplified ROS generation was the dominant factor in provoking a strong immune response at a physiological tolerable temperature below 40 °C in a hypoxic tumor microenvironment. This was supported by the exposure of calreticulin (CRT) on 83% of the 4T1 breast cancer cell surface, direct promotion of macrophage polarization to pro-inflammatory M1 phenotypes, and further elevation of tumor-infiltrating T lymphocytes. As a result of the dual action of magnetothermal effect and ROS-related immunologic effect, impressive systemic therapeutic efficacy was attained at a low dosage of 3 mg Fe/kg with two AMF treatments, as compared to that of MTT (high dosage of 6-18 mg/kg under four to eight AMF treatments). The MTD therapy reported here has highlighted the inadequacy of conventional MTT that solely relies on the heating effect of the MNPs. Thus, by employing a ROS-mediated immunologic effect, future cancer magnetotherapies can be designed with greatly improved antitumor capabilities.
在这项研究中，通过将磁热效应与活性氧（ROS）相关的免疫效应相结合，引入一种磁热动力学（MTD）疗法作为有效的系统癌症治疗方法，以克服当前磁热疗法（MTT）疗效有限的障碍。这种方法是通过开发一种精心设计的亚铁磁涡旋畴氧化铁纳米环和氧化石墨烯（FVIOs-GO）杂化纳米颗粒作为有效的 MTD 剂来实现的。这种 FVIOs-GO 纳米平台具有高热转换效率，并且在交变磁场（AMF）下被证明能够产生显著放大的 ROS 水平。和 结果均表明，在缺氧肿瘤微环境中，在生理耐受温度（低于 40°C）下，放大的 ROS 生成是引发强烈免疫反应的主要因素。这得到了以下事实的支持：在 4T1 乳腺癌细胞表面有 83%的细胞暴露钙网蛋白（CRT），直接促进巨噬细胞向促炎 M1 表型极化，并进一步增加肿瘤浸润性 T 淋巴细胞。由于磁热效应和 ROS 相关免疫效应的双重作用，以 3mg Fe/kg 的低剂量进行两次 AMF 治疗即可实现令人印象深刻的全身治疗效果，而 MTT（在四次至八次 AMF 治疗下以 6-18mg/kg 的高剂量）则无法实现。这里报道的 MTD 治疗方法强调了传统 MTT 的不足，传统 MTT 仅依赖于 MNPs 的加热效应。因此，通过采用 ROS 介导的免疫效应，可以设计出具有大大提高抗肿瘤能力的未来癌症磁疗方法。
