Heat-Generating Iron Oxide Multigranule Nanoclusters for Enhancing Hyperthermic Efficacy in Tumor Treatment

Abstract

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.

Superparamagnetic iron oxide nanoparticles for magnetic hyperthermia: recent advancements, molecular effects, and future directions in the omics era

“…Jeon et al studied the in vivo efficacy of magnetic hyperthermia induced with PEG-coated iron oxide multigranule nanoclusters (PEG-MGNCs) compared to PEGylated single iron oxide nanoparticles (PEG-NPs) in SCC7 (mouse squamous cell carcinoma) tumour-bearing mice. 99 The AMF stimulation (19.5 kA/m, 389 kHz) was induced after 24 and 48 h from nanoparticles injection and lasted 30 min. As can be seen from Figure 4.a, at the end of the stimulus, the temperature of the tumour tissue treated with PEG-MGNCs reached ≈ 45°C.…”

An Overview of Micronanoswarms for Biomedical Applications

“…(b6) Tumor changes in mice before and after MH. Adapted with permission from ref . Copyright 2020 American Chemical Society.…”

“…Jeon et al . developed iron oxide nanoparticle-based swarms coated with polyethylene glycol for tumor MH in vivo . As shown in Figure b6, it can be found that the tumor growth was suppressed after the swarms were heated under MH from the differences of tumor volume in mice.…”

The Multifunctionally Graded System for a Controlled Size Effect on Iron Oxide–Gold Based Core-Shell Nanoparticles

“…Integration of magnetic iron oxide (Fe 3 O 4 ) and Au NPs can be used in hyperthermia [ 10 ], catalysis [ 11 ], and surface modification [ 12 ]. Furthermore, Fe 3 O 4 NPs have been used as carriers for cell imaging [ 13 ] and drug delivery systems [ 14 ] due to their apparent superparamagnetism, high specific surface area, significant colloidal stability, and excellent biocompatibility [ 15 , 16 ]. An Au coating onto magnetic NPs is another appealing hybrid system [ 17 , 18 ].…”