Magnetic Nanoparticles in Cancer Treatment

Although nanomedicine may sound like something out of a science fiction film, it is already being put to use in treating a range of human illnesses. Magnetic nanoparticles are currently in development as a promising new type of cancer treatment that uses nanoparticles to selectively heat tumors to temperatures high enough to kill cancer cells without harming healthy cells.¹ This destroys tumors as well as activates the immune system to attack other cancer cells throughout the body.

**Figure 1**: A ferrofluid forming peaks when brought close to a magnet. (image by Steve Jurvetson)

This intriguing new treatment is called magnetic-mediated hyperthermia (MMH). Hyperthermia, which means high temperature, has been proposed throughout history as a way to treat many diseases. Hippocrates (a Greek physician known as the father of western medicine – the Hippocratic Oath is named after him) said, “those diseases which medicines do not cure, the knife cures; those which the knife cannot cure, fire cures; those which fire cannot cure, are to be reckoned wholly incurable.” The problem, though, is that cells must be heated to 43 °C (109 °F) to be destroyed.¹ Of course, since our normal body temperature is 98.6 °F, a human body cannot be heated that much without undesirable consequences. That means that in order to put hyperthermia to use, doctors must be able to selectively heat only the cells they want to kill, while leaving all the other parts of the body untouched.

This is where the nanoparticles come in.

There is a type of magnetic fluid, known as a ferrofluid, that is made from iron oxide particles (commonly magnetite²) that are less than 100 nm in size. These ferrofluids are called superparamagnetic which means that they are not magnetized until an external magnetic field is applied to them. A ferrofluid looks like a regular liquid until it is brought close to a magnet, when it suddenly organizes into unique peaks and valleys (see Figure 1 above).

Due to the nanoparticles’ size, ferrofluid can be injected directly into cancer cells and will spread through a tumor without dispersing widely around the body. Then, an alternating magnetic field is applied to the patient. This alternating magnetic field creates small currents running through the ferrofluid, and these small currents give off heat due to resistance. Think of your phone charger heating up when in use – this is a similar idea except the heat is used as energy rather than wasted heating up the air or furniture around your charger.

**Figure 2**: Any heat generated by the currents in your phone as it charges usually just dissipates into the surrounding environment. (image by Ed Gregory)

At a certain temperature called the Curie Point the ferrofluid becomes disordered again, and stops heating up. This phenomenon makes the nanoparticles self-regulating: the hyperthermia essentially turns itself off when the nanoparticles reach their Curie Point. By using materials designed with Curie Points at a safe maximum temperature (122 – 158 °F) doctors don’t have to closely monitor the patient’s internal temperature throughout the treatment.¹

Magnetic-mediated hyperthermia can be used to treat local tumors, but it also ramps up the immune system to find and destroy distant cells. This is because cancer cells produce more heat shock proteins (HSPs) than normal cells. HSPs help repair damaged proteins when cells are exposed to high heat or toxins. When cancer cells are heated to high temperatures from the magnetic-mediated hyperthermia, they produce HSPs in high quantities. The HSPs in turn bind to antigens (molecules or proteins that trigger an immune response). When some cells are destroyed by the heat, their HSPs and antigens are released into the body. That then attracts cells from the immune system, which interact with the HSP-antigen complex and use them to hunt down other cancer cells that were not damaged by the initial heating.²

**Figure 3**: Example of a heat shock protein (HSP) (image by Emw)

Nanoparticles can also be used to combine hyperthermia with other cancer treatments like chemotherapy. Small molecules called ligands can coat a nanoparticle’s surface to selectively target receptors or enzymes in certain cancer cells. Ligands improve the stability of magnetic nanoparticles in biological materials and can also be used to direct chemotherapy drugs into tumors. For instance, negatively charged magnetic nanoparticles and positively charged cisplatin molecules (a chemotherapy drug) are attracted to each other to form a nanoparticle-drug complex. Once this nanoparticle-drug complex is targeted to cancer cells, an alternating magnetic field is applied. The heat produced both kills the cancer cells and releases the drugs from the nanoparticles directly inside the cancer cells! Studies show that hyperthermia and chemotherapy are significantly more effective in combination than when used separately.¹

**Figure 4**: Cisplatin crystals (not attached to any nanoparticles) (image by the National Cancer Institute)

The really exciting part of the MMH treatment is that it has been shown to be effective with only minor side effects. In animal studies as well as phase I and II trials in humans, MMH has killed tumors in types of cancer that are typically extremely difficult to treat, such as glioblastoma (a type of brain cancer), with only minor side effects. The skin next to tumors is slightly warmed during treatment, but otherwise, many types of magnetic nanoparticles have low toxicity.³ Also, chemotherapy drugs directed into cancer cells by nanoparticles do less damage to healthy cells.¹ Overall, the potential benefits of MMH are judged to outweigh the side effects, and MMH is an acceptable treatment according to medical ethical considerations.³

Further research is needed on the effects of applying magnetic fields to humans as well as ways to use fewer nanoparticles while reaching higher temperatures.⁴ Some materials have higher heating capacity than others, which is good as long as the materials are also nontoxic and biocompatible. Despite these hurdles, MMH has been approved for use in Germany to treat brain cancer under the name MagForce NanoTherm™ therapy.¹ This new technology shows great promise in cancer treatment especially when combined with treatments already in use.

EDUCATIONAL RESOURCES

UW-Madison Materials Research Science and Engineering Center: Nanomedicine: Problem-Solving to Treat Cancer (middle school)
Science Buddies: “Can Nanotechnology Help Us Clean Up Oil Spills…?” ferrofluid activity

REFERENCES

Etheridge, M. L. Understanding the Benefits and Limitations of Magnetic Nanoparticle Heating for Improved Applications in Cancer Hyperthermia and Biomaterial Cryopreservation. Dissertation, University of Minnesota – Twin Cities, 2013.
Kobayashi, T., Ito, A., & Honda, H. Magnetic Nanoparticle-Mediated Hyperthermia and Induction of Anti-Tumor Immune Responses. Chapter in Hyperthermic Oncology from Bench to Bedside, pp. 137-150. Springer Singapore, 2016. doi: 10.1007/978-981-10-0719-4_13
Müller, S. Magnetic fluid hyperthermia therapy for malignant brain tumors—an ethical discussion. Nanomedicine: Nanotechnology, Biology and Medicine, 2009, 5 (4) 387–393. doi: 10.1016/j.nano.2009.01.011
Zhao, L.-Y. et al. Magnetic-mediated hyperthermia for cancer treatment:
Research progress and clinical trials. Chinese Physics B, 2013, 22 (10) 108104. doi: 10.1088/1674-1056/22/10/108104