The development of heat-generating magnetic nanostructures is critical for the effective management of tumors using magnetic hyperthermia. Herein, we demonstrate that polyethylene glycol (PEG)-coated iron oxide (magnetite, Fe3O4) multigranule nanoclusters (PEG-MGNCs) can enhance the efficiency of hyperthermia-based tumor suppression in vitro and in vivo. MGNCs consisting of granules (crystallites) measuring 22.9 nm in diameter were prepared via the hydrothermal polyol method, followed by the surface modification of MGNCs with PEG-dopamine. The freshly prepared PEG-MGNCs exhibit 145.9 ± 10.2 nm diameter on average under aqueous conditions. The three-dimensional structures of PEG-MGNCs enhance the hyperthermic efficacy compared with PEGylated single iron-oxide nanoparticles (NPs), resulting in severe heat damage to tumor cells in vitro. In the SCC7 tumor-bearing mice, near-infrared fluorescence dye (Cy5.5)-labeled PEG-MGNCs are successfully accumulated in the tumor tissues because of NP-derived enhanced permeation and retention effect. Finally, the tumor growth is significantly suppressed in PEG-MGNC-treated mice after two-times heat generation by using a longitudinal solenoid, which can generate an alternating magnetic field under high-frequency (19.5 kA/m, 389 kHz) induction. This study shows for the first time that the PEG-MGNCs greatly enhance the hyperthermic efficacy of tumor treatment both in vitro and in vivo.
Bibliographical noteFunding Information:
This research was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (2019R1A2C3006587), the Basic Science Research Program through the Research Foundation of Korea (NRF) funded by the Ministry of Education (2019R1I1A1A01062020), the KU-KIST Graduate School of Converging Science and Technology (Korea University), and the Intramural Research Program of KIST. We thank the Institute for Basic Science (IBS) Center for Neuroscience Imaging Research (IBS-R015-D1) for providing MRI time and professional technical support.
Copyright © 2020 American Chemical Society.
- high frequency
- iron oxide nanoparticle
- multigranule nanocluster
- polyethylene glycol