Graphene Oxide-Grafted Magnetic Nanorings Mediated Magnetothermodynamic Therapy Favoring Reactive Oxygen Species-Related Immune Response for Enhanced Antitumor Efficacy.

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 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 significantly amplified ROS level under 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 oC in a hypoxic tumor microenvironment. This was supported by the exposure of calreticulin (CRT) on 83% 4T1 breast cancer cell surface, direct promotion of macrophages 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 2 AMF treatments, as compared to that of MTT (high dosage of 6-18 mg/kg under 4-8 AMF treatments). The MTD therapy reported here has highlighted the inadequacy of conventional MTT that solely relies on heating effect of the MNPs. Thus, by employing ROS mediated immunologic effect, future cancer magnetotherapies can be designed with greatly improved antitumor capabilities.