Attempts to control the release of molecules through magnetothermal effects have attracted notice ever since the first observations of temperature changes in magnetic nanoparticles in response to magnetic fields. However, most studies of this approach have focused on the release of non-therapeutic fluorescence molecules, and relatively few reports have focused on magnetic-field-controlled thermal release of drugs, such as paclitaxel and doxiciclin.

"Until now, two types of devices containing liposomes as carriers for gemcitabine have been studied," explains Roberta V Ferreira, a researcher at the Federal Center of Technological Education of Minas Gerais in Brazil, and lead author in the report of this current research. These previous studies looked at gemcitabine in bubble-shaped lipid carriers – ‘liposomes’ - or magnetoliposomes (which contain magnetic nanoparticles). However, these structures were primarily designed to protect the drug from being metabolized by the body before reaching the tumour. The role of the magnetic nanoparticles in the magnetoliposomes was to provide a means of leading the drug to the tumour region.

Ferreira and colleagues at the Federal University of Minas-Gerais, the Federal University of the Jequitinhonha and Mucuri Valleys, and the Federal University of Piauí in Brazil prepared magnetoliposomes consisting of magnetite nanoparticle cores and gemcitabine encapsulated by a phospholipid bilayer. The structure of the thermally sensitive liposomes changes when heated above body temperature, releasing the drug inside. Their work is the first demonstration of the magnetic-field-controlled thermal release of gemcitabine from magnetoliposomes.

The increased sensitivity to temperature in tumour cells compared to healthy cells means that the temperature change caused by the magnetic nanoparticles can also be used as an anticancer therapy. In fact this was the initial focus of the team’s research before they incorporated drug release to yield dual-therapeutic returns.

Hot target

While the ability to direct magnetic nanoparticles with a magnetic field is one of the advantages of using them in drug carriers, as Ferreira points out there are other approaches that can be harnessed to specifically target the tumour.

"Another option that is more sophisticated consists of conjugating the liposomal surface with targeting moieties (small-molecule ligands, peptides and monoclonal antibodies) that are able to recognize specific receptors on the tumour cell surface," says Ferreira. "However, the most important effect that can be explored with our device is the EPR effect."

The "EPR effect" – enhanced permeability and retention – is a well established phenomenon that results from the differences in cell coverage on blood vessel walls. Cells are spaced 15-30 nm apart for healthy tissue, versus 100-780 nm apart for tumour tissue. As a result, drug carrier particles between 50 nm and 300 nm can pass through blood vessel walls more readily for tumour tissue, and hence accumulate there.

Broadening horizons

One of the main challenges in developing the gemcitabine magnetoliposomes is the ready oxidation of the magnetic nanoparticles, which damages their performance. Ferreira and her colleagues developed careful procedures for producing the formulations without exposing the magnetic nanoparticles to oxidizing agents, and are now looking at how broadly they can be applied.

"The most interesting characteristic of these liposome devices is that we can incorporate lipophilic and hydrophilic drugs," Ferreira tells "This opens opportunities to encapsulate a wide range of drugs - our group has already begun developing similar devices with the drug paclitaxel."

The researchers are also experimenting with in vitro assays of two different types of tumour cell to demonstrate the efficacy of their combined therapy.

Full details of the work are reported in Nanotechnology.