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

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.

Persistent Regulation of Tumor Hypoxia Microenvironment via a Bioinspired Pt‐Based Oxygen Nanogenerator for Multimodal Imaging‐Guided Synergistic Phototherapy

“…[ 59 ] PDT has been demonstrated to induce immunogenic cell death (ICD) and activate an adaptive immune response against tumor‐associated antigens. [ 60 ] As PDT is a typical oxygen‐consuming process whose effect can be severely limited by tumor hypoxia, thus the oxygen supplied nanoparticles can elicited ICD upon abundant ROS in PDT. Similarly, PTT has been shown to trigger the thermal ablation‐induced tumor ICD and cause the release of tumor antigens and endogenous adjuvants (e.g., heat shock proteins and damaged‐associated molecular patterns) to stimulate the immune responses.…”

The Prognostic Role of Glutathione Peroxidase 1 and Immune Infiltrates in Glioma Investigated Using Public Datasets

“…Reactive oxygen species (ROS), which include hydroxyl radicals, superoxide, and hydrogen peroxide, can be produced by enzymatic and mitochondrial sources in normal and tumor cells [ 30 , 31 ]. If they continue to accumulate in cytoplasm and mitochondria, they may cause oxidative damage to proteins, DNA, RNA, and organelles [ 32 , 33 ].…”

Recent Advances in Hyperthermia Therapy‐Based Synergistic Immunotherapy

“…designed a graphene oxide (GO)‐grafted ferrimagnetic vortex‐domain iron oxide nanoring (FVIOs) nanohybrid and conjugated it with Cys‐Arg‐Glu‐Lys‐Ala (CREKA) peptide to improve tumor accumulation ( Figure a). [ 132 ] Such FVIO‐GO‐CREKA nanocomposites exhibited high magnetic thermal conversion efficiency and amplified ROS generation via a thermal‐enhanced Fenton reaction under AMF. The nanocomposite‐induced magnetothermodynamic therapy was able to provoke ICD, boost macrophage polarization to tumoricidal M1 phenotypes, and elevate the tumor‐infiltrating T lymphocytes in TME (Figure 14b).…”

“…Inhibited bilateral tumor growth [128] MHT, CDT FVIO, graphene oxide Induced by PTT and ROS Not applicable 4T1 Inhibited tumor growth [132] MHT, PDT Some studies have demonstrated that some nanoparticles have potential risks; for instance, dendritic nanomedicine can cause permeability damage and cell membrane rupture. The pharmacological and toxicological analyses of nanomedicine have shown that once the particle size is reduced to a certain extent, the toxicity would increase dramatically.…”