Recent Advancements of Magnetic Nanomaterials in Cancer Therapy

Abstract

Magnetic nanomaterials belong to a class of highly-functionalizable tools for cancer therapy owing to their intrinsic magnetic properties and multifunctional design that provides a multimodal theranostics platform for cancer diagnosis, monitoring, and therapy. In this review article, we have provided an overview of the various applications of magnetic nanomaterials and recent advances in the development of these nanomaterials as cancer therapeutics. Moreover, the cancer targeting, potential toxicity, and degradability of these nanomaterials has been briefly addressed. Finally, the challenges for clinical translation and the future scope of magnetic nanoparticles in cancer therapy are discussed.

Keywords: cancer therapy; immunotherapy; magnetic nanoparticles (MNPs); multifunctionality; theranostics; toxicity.

Figure 1

Evaluation of in vivo therapeutic efficacy. (a) Treatment scheme of DoxSMNPs in mouse and results of the tumor volume change over the course of the treatment (15 days) in DLD-1 xenografted mice (n = 3) treated with DoxSMNPs (w/and w/o application of AMF) and other controls (AMF only and PBS only). All injections were done on day 0 (and day 7 for the double injection group) when the tumor volume reached 100 mm³; AMF application was performed at 36 h post-injection. The best tumor suppression result was observed in the group treated with a double injection of DoxSMNPs with AMF application. The group treated with a single injection of DoxSMNPs with AMF and the other control groups (i.e., treated with DoxSMNPs only, AMF only and PBS) show either a smaller degree or none of tumor suppression effects (** p ≤ 0.01; *** p ≤ 0.001). (b) Tumor images of groups treated with DoxSMNPs w/and w/o application of AMF and other controls, before treatment (left panels) and at the termination point (right panels). * The termination point of the experiment occurred either on day 15 or when the tumor volume reached 1500 mm³. The figure was reproduced from [59] after permission from John Wiley and Sons.

Figure 2

Tumor ablation therapies with iron oxide nanoparticles (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. The figure was reproduced from [31] after permission from Elsevier.

Figure 3

(a) Photograph (left) and thermal image (right) of a mouse 24 h after intravenous injection of folic acid conjugated pegylated superparamagnetic iron oxide nanoconjugates (FA-PEG-SPION NCs) under an AC magnetic field with H = 8 kA/m and f = 230 kHz. (b) Tumor-growth behavior and (c) survival period of mice without treatment and treated by intravenous injection of FA-PEG-SPION NCs, application of an alternating current (AC) magnetic field, and application of an AC magnetic field 24 h after intravenous injection of FA-PEG-SPION NCs (n = 5). (d) Photographs of mice 35 days after treatment. The figure was reproduced from [97] after permission from Ivy Spring.

Figure 4

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. The figure was reproduced from [105] after permission from Elsevier.

Figure 5

Nanoparticle size, shape and surface charge dictate biodistribution among the different organs including the lungs, liver, spleen and kidneys. (a) Spherical particles, including gold/magnetic nanoparticles, liposomes and polymeric micelles/NPs can vary in size and display disparate in vivo fates. Large rigid particles with diameters > 2000 nm accumulate readily within the spleen and liver, as well as in the capillaries of the lungs. Nanoparticles in the range of 100–200 nm have been shown to extravasate through vascular fenestrations of tumors (the EPR effect) and escape filtration via liver and spleen. As size increases further than 150 nm, extra NPs are captured within the liver and spleen. Small-sized NPs (<5 nm) are filtered out by the kidneys. (b) Novel 'top-down' and 'bottom up' fabrication tools have allowed the investigation of various geometries of NPs, including cylindrical and discoidal shapes, which have been shown to demonstrate distinct effects on pharmacokinetics and biodistribution. Various NPs shapes show exclusive flow characteristics that significantly change circulating lifetimes, cell membrane interactions and macrophage uptake, which in turn manipulate biodistribution between the different organs. (c) Charge of NPs stemming from distinct surface chemistries influences opsonization, circulation times, and interaction with local macrophages of organs comprising the mononuclear phagocytic system (MPS), with positively charged particles more prone to sequestration by macrophages in the lungs, liver, and spleen. Neutral and a little negatively charged NPs have longer circulation lifetimes and lower accumulation in the above mentioned organs of the MPS. In both b and c, the size of the NPs is in the range from 20–150 nm. Individual panels correspond to in vivo fates of NPs, taking into account singular design parameters of size, shape, and surface charge independent of one another, and for this reason, respective scales differ from one panel to the next. It is vital to note that in vivo biodistribution will vary based on the interaction of various these parameters. The figure and figure caption was reproduced and adapted from [110] after permission from NPG, respectively.