Ferrimagnetic Vortex Nanoring-Mediated Mild Magnetic Hyperthermia Imparts Potent Immunological Effect for Treating Cancer Metastasis.

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.

Synthesis of Ferromagnetic Fe0.6 Mn0.4 O Nanoflowers as a New Class of Magnetic Theranostic Platform for In Vivo T1 -T2 Dual-Mode Magnetic Resonance Imaging and Magnetic Hyperthermia Therapy.

Uniform wüstite Fe0.6 Mn0.4 O nanoflowers have been successfully developed as an innovative theranostic agent with T1 -T2 dual-mode magnetic resonance imaging (MRI), for diagnostic applications and therapeutic interventions via magnetic hyperthermia. Unlike their antiferromagnetic bulk counterpart, the obtained Fe0.6 Mn0.4 O nanoflowers show unique room-temperature ferromagnetic behavior, probably due to the presence of an exchange coupling effect. Combined with the flower-like morphology, ferromagnetic Fe0.6 Mn0.4 O nanoflowers are demonstrated to possess dual-modal MRI sensitivity, with longitudinal relaxivity r1 and transverse relaxivity r2 as high as 4.9 and 61.2 mm(-1) s(-1) [Fe]+[Mn], respectively. Further in vivo MRI carried out on the mouse orthotopic glioma model revealed gliomas are clearly delineated in both T1 - and T2 -weighted MR images, after administration of the Fe0.6 Mn0.4 O nanoflowers. In addition, the Fe0.6 Mn0.4 O nanoflowers also exhibit excellent magnetic induction heating effects. Both in vitro and in vivo magnetic hyperthermia experimentation has demonstrated that magnetic hyperthermia by using the innovative Fe0.6 Mn0.4 O nanoflowers can induce MCF-7 breast cancer cell apoptosis and a complete tumor regression without appreciable side effects. The results have demonstrated that the innovative Fe0.6 Mn0.4 O nanoflowers can be a new magnetic theranostic platform for in vivo T1 -T2 dual-mode MRI and magnetic thermotherapy, thereby achieving a one-stop diagnosis cum effective therapeutic modality in cancer management.

Magnetic stent hyperthermia for esophageal cancer: an in vitro investigation in the ECA-109 cell line.

Magnetic stent hyperthermia (MSH) is a novel approach for targeted thermotherapy for esophageal cancer, which is based on the mechanism that inductive heat can be generated by the esophageal stent upon exposure under an alternative magnetic field (AMF). A positive effect of MSH on esophageal cancer has been demonstrated, however, there is no study on the in vitro effects of heating treatment or of the effects of AMF exposure on human esophageal cancer cells. This study aimed to investigate the effect of MSH and of AMF exposure in esophageal cancer cells. Inductive heating characteristics of esophageal stents were assessed by exposing the stents under AMF. A rather rapid temperature rise of the Ni-Ti stent when subjected to AMF exposure was observed and the desired hyperthermic temperature could be controlled by adjusting the field parameter of the AMF. Human esophageal squamous carcinoma (ESCC) ECA-109 cells were divided into four groups: the control group, the water-bath heating group, the MSH group and the AMF exposure group. Hyperthermic temperatures were 43, 48 and 53˚C and the treatment time was in the range of 5-30 min. The MTT assay, apoptotic analysis and TUNEL staining were applied in the current investigation. Exposure of ECA-109 cells under AMF with a field intensity of 50 to 110 kA/m had negligible effect on cell viability, cell necrosis and apoptosis. Hyperthermia had a remarkable inhibitory effect on the cell viability and the effect was dependent on the thermal dose (temperature and time). The optimal thermal dose of MSH for ECA-109 cells was 48˚C for 20-30 min. The study also elucidated that there was a difference in the effects on cell necrosis and apoptosis between the heating mode of water bath and MSH. The data suggest that MSH may have clinical significance for esophageal cancer treatment.