201. Graphene Oxide-Grafted Magnetic Nanorings Mediated Magnetothermodynamic Therapy Favoring Reactive Oxygen Species-Related Immune Response for Enhanced Antitumor Efficacy
- Author
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Xiaowei Ma, Yuan He, Xiao-Li Liu, Kejian Shi, Tingbin Zhang, Haiming Fan, Xing-Jie Liang, Bin Yan, Wangbo Jiao, Shizhu Chen, and Yao Li
- Subjects
Surface Properties ,Macrophage polarization ,Oxide ,General Physics and Astronomy ,Antineoplastic Agents ,Breast Neoplasms ,02 engineering and technology ,010402 general chemistry ,Ferric Compounds ,01 natural sciences ,Rats, Sprague-Dawley ,Mice ,chemistry.chemical_compound ,Immune system ,In vivo ,Cell Line, Tumor ,Tumor Microenvironment ,medicine ,Animals ,General Materials Science ,Particle Size ,chemistry.chemical_classification ,Mice, Inbred BALB C ,Reactive oxygen species ,biology ,Chemistry ,General Engineering ,Cancer ,021001 nanoscience & nanotechnology ,medicine.disease ,In vitro ,Rats ,0104 chemical sciences ,Magnetic Fields ,RAW 264.7 Cells ,biology.protein ,Biophysics ,Nanoparticles ,Thermodynamics ,Female ,Graphite ,Reactive Oxygen Species ,0210 nano-technology ,Calreticulin - Abstract
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 in vitro and in vivo 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 in vivo 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.
- Published
- 2020
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