Magnetite nanoparticles for cancer diagnosis, treatment, and treatment monitoring: recent advances

Abstract

The development of nanoparticles (NPs) for use in all facets of oncological disease detection and therapy has shown great progress over the past two decades. NPs have been tailored for use as contrast enhancement agents for imaging, drug delivery vehicles, and most recently as a therapeutic component in initiating tumor cell death in magnetic and photonic ablation therapies. Of the many possible core constituents of NPs, such as gold, silver, carbon nanotubes, fullerenes, manganese oxide, lipids, micelles, etc., iron oxide (or magnetite) based NPs have been extensively investigated due to their excellent superparamagnetic, biocompatible, and biodegradable properties. This review addresses recent applications of magnetite NPs in diagnosis, treatment, and treatment monitoring of cancer. Finally, some views will be discussed concerning the toxicity and clinical translation of iron oxide NPs and the future outlook of NP development to facilitate multiple therapies in a single formulation for cancer theranostics.

Fig.1

Schematic illustration of a full-suite theranostic NP. The magnetite core serves as an MRI contrast agent and heat source for magnetic hyperthermia, and a polymer coating increases biocompatibility, mitigates RES uptake, and allows for facile functionalization with chemotherapeutic, biotherapeutic, optical enhancement, and targeting moieties.

Fig. 2

Enhanced CT and MRI contrast from dextran coated bismuth-iron oxide nanoparticles in a mouse model. (a) 3D volume rendered CT images of a mouse, pre- and 5, 30, 60, and 120 minutes post-injection. (b) CT images of a mouse thorax acquired at different time points; the arrow indicates the heart. (c) CT images of mouse groin acquired at different time points; the arrow indicates the bladder. (d) CT attenuation change of different organs over time, post-injection. (e) In vivo MRI of the mouse liver before and 2 hours after injection. (f) Quantitation of the MRI signal intensity in the liver compared for pre- and post-injection images. Adapted from Ref. with permission of The Royal Society of Chemistry.

Fig. 3

Monitoring drug delivery with SPIONs through T₁ and T₂ changes. The drugs Flutax1, DiR, and Doxorubicin increased T₂ (a) and T₁ (b) values as compared to native iron oxide (denoted as vehicle). (c) Gradual addition of Flutax1 within the iron oxide NP coating increased the formulation’s T₁ and T₂ signals. As Doxorubicin was released from the NP in acidified buffers, the T₂ (d) and T₁ (e) values decreased. Adapted from Ref. with permission from Nature Publishing Group.

Fig. 4

Tumor ablation therapies with iron oxide NPs. (a) In magnetic hyperthermia, an alternating magnetic field causes iron oxide NPs to generate heat, inducing tumor necrosis. (b) In photothermal ablation, light absorbed by NPs is converted to thermal energy causing cell death in the vicinity. (c) For photodynamic therapy, photosensitizing agents attached to NPs are activated by an external light source to create singlet oxygen species that are cytotoxic to cells.

Fig. 5

Magnetite NP-induced magnetic hyperthermia and its effect on the growth of solid tumors in mice. (a) Thermographic infrared photographs taken during exposure to an alternating magnetic field (at the starting time, 5, and 30 minutes of exposure) of a mouse intratumorally injected with iron oxide NPs. The scale bar on the right indicates the color code of the surface temperature. (b) Graph of the temperature evolution of NP-injected tumor control sites; note that only the tumor site injected with NPs (yellow) heated significantly while other tissues remained at normal temperatures. (c) Tumor growth curves of non-injected mice (Control), mice injected with NPs and exposed to an alternating magnetic field on day 0, day 1, and day 2 (3x HT), mice injected intravenously with Doxorubicin (Doxo), mice injected with Doxorubicin and NPs and exposed to an alternating magnetic field (Doxo + 3x HT). Tumor volumes are normalized to the tumor volume on day 0 when the injection was made. Adapted from Ref. with permission from the American Chemical Society.

Fig. 6

Photodynamic therapy with iron oxide nanoparticles conjugated with photosensitizing agent Ce6. (a) A schematic drawing to illustrate in vivo magnetic tumor targeting. (b) In vivo fluorescence image of a 4T1 tumor bearing mouse. (c) In vivo T₂-weighted MR images of a mouse taken before injection (upper) and 24 h post injection (bottom). White and red arrows point to tumors without and with a magnet attached, respectively. (d) Ce6 fluorescence signal intensities in magnetic field (MF) targeted and non-targeted tumor regions. (e) T₂-weighted MR signals of untreated, MF targeted and non-targeted tumors. (f) Tumor growth curves of different groups of tumors after various treatments indicated. Error bars were based on SD of six tumors per group. MF: magnetic field; L: light. (g) Representative photos of mice after various treatments. White and red arrows point to tumors without and with magnetic targeting, respectively. Adapted from Ref. with permission from The Royal Society of Chemistry.