Localized hyperthermia involves using heat (temperatures above 43 °C) to clinically treat solid tumours as it boosts the cytotoxic effects of chemotherapy or radiotherapy and also increases the permeability of tumour cells to drugs. It works because cancer cells are more sensitive to heat than healthy ones. Indeed, the technique has already been tested on many types of human cancer, including recurrent malignant melanoma, lymph node metastasis, glioblastoma, cervical carcinoma, and head and neck cancers.

Magnetic hyperthermia works by introducing magnetic particles into tumour cells, and then heating these particles using an applied magnetic field. Enough heat is generated to kill the cancer cells and the latest techniques allow heat to be applied to more precise areas than before. However, the problem is that it is difficult to transport ferrofluid or magnetic nanoparticles to deeply lying tumours. Previous experiments involved directly injecting milligram amounts of these ferromagnetic materials into cancer cells or attaching special ligands to the nanoparticles before injection – all with limited success.

Trojan Horse
Now, Deryl Troyer and colleagues Stefan Bossmann and Viktor Chikan have shown for the first time that neural progenitor cells can act as a sort of "Trojan horse" for magnetic nanoparticles. The cells, which are precursors to neurons or glia – often also called "neural stem cells" – can be preloaded ex vivo with core/shell magnetic Fe/Fe3O4 bimagnetic nanoparticles and intravenously injected into mice with melanomas. After several days, after the cells have had enough time to home in onto the tumour, the researchers apply an external AC magnetic field. The cancer cells are destroyed after several cycles of this process because the tumour proteome is denatured by the heat generated by the magnetic field.

"Our technique allows cancer-cell targeting via an active process, since the delivery cells are attracted to the tumours by chemokine or cytokine gradients," explained Troyer. "The technique could be a platform for combination with cancer gene therapy – for example, the delivery cells could also be engineered to express an anticancer protein – and at the same time transport the magnetic nanoparticles to the tumour for subsequent magnetic hyperthermia."

The team will now test how good the delivery cells are at targeted hyperthermia combined with a chemotherapeutic drug tethered to the magnetic nanoparticles to reduce pancreatic cancers in mice. Here, the active tumour-fighting drug will be released by one or several enzymes that are overproduced by tumours. "We also have the ability to engineer stem cells to produce drug-releasing enzymes," Troyer told nanotechweb.org.

The work was published in ACS Nano.