Ultrasmall Fe₃O₄@Au Composite Nanoparticles With Different Sizes of Fe₃O₄ for Magnetic Hyperthermia

We present the synthesis and characterization of ultrasmall iron oxide/gold composite nanoparticles (Fe3O4@Au NPs) with different Fe3O4 sizes, along with an evaluation of their heating efficiency for potential use in magnetic hyperthermia (MH) applications. The Fe3O4 NPs of approximately 5, 10, and 13 nm were synthesized using the thermal decomposition method, followed by gold deposition via the reduction of gold acetate at 190 °C. The morphology, structure, and magnetic properties of as-prepared Fe3O4 and their Fe3O4@Au NPs were determined and characterized by transmission electron microscope (TEM), energy dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), and vibrating sample magnetometer (VSM) analyses. The magnetization of Fe3O4 NPs increased with increasing their size, reaching 74.7 emu/g for ~13 nm NPs. The Fe3O4@Au NPs contained 94.3%, 96.3%, and 77.0% Au (wt%) for Fe3O4~5, Fe3O4~10, and Fe3O4~13 nm@Au, respectively, estimated from the magnetization values. The heating efficiency specific absorption rate (SAR) demonstrated an increasing trend with Fe3O4 size, reaching maximum values of 136.7 and 23.4 W/g under a magnetic field of 25.7 kA/m and 267 kHz for Fe3O4~13 nm and Fe3O4~13 nm@Au NPs, respectively. These results indicate high heating efficient capabilities and the potential use of NPs for MH applications.

I. Introduction

Theranostic agents and their applications using iron oxide/gold (Fe3O4@Au) composite magnetoplasmonic nanoparticles (Fe3O4@Au NPs) are of great interest in cancer therapy owing to their potential for targeted delivery, multimodal imaging diagnosis, and magnetic hyperthermia (MH) and/or photothermal therapies [1], [2], [3], [4]. MH has gained considerable attention as a promising cancer therapy with fewer invasiveness and side effects compared to conventional therapies, following the pioneering work by Gilchrist et al. in the 1950 s [5]. In this therapy, the heat generated from tumor-localized magnetic nanoparticles (MNPs) exposed to an externally applied magnetic field induces apoptosis or necrosis of cancer cells [6], [7]. Additionally, MH can sensitize tumor cells to adjuvant therapies, such as radiotherapy and chemotherapy. Extensive efforts have been devoted to the development of the MNPs, monitoring their position and temperature, and controlling their temperature in the tumor region [8], [9], [10], [11], [12], [13], [14], [15]. Although successful clinical trials have been conducted for glioblastoma tumors [16], [17], there are still numerous challenges to making MH a standard part of cancer treatment. The primary challenge is to enhance the heating performance of highly biocompatible MNPs, which can reduce the amount of injected MNPs required for effective therapeutic performance and subsequently minimize potential toxicity. The heating performance of MNPs strongly depends on their intrinsic properties, such as composition, size, polydispersity, shape, coating material, concentration, injection volume, structure (e.g., single-core, multicore, chainlike), and additional extrinsic properties, including the frequency and strength of the externally applied magnetic field, as well as the viscosity and blood perfusion in the tumor tissue [18], [19], [20], [21], [22], [23], [24], [25], [26], [27]. Notably, the applied magnetic field could also lead to undesirable nonspecific heating of healthy tissues via Joule heating. The upper limit of the magnetic field that can be safely tolerated by humans is not accurately defined. Recently, an upper limit was proposed with for a smaller diameter of the body region being exposed to the alternating magnetic field (e.g., breast cancer) [6].