One of nanotechnology's greatest selling points in the medical arena is the ability to target and destroy cancerous tissue without the negative side effects of systemically delivered therapies. But a big stumbling block is exactly how to concentrate those nano-sized therapies at the disease site. An international collaboration of companies along with researchers at University of Dundee (UD; Scotland) are tackling that dilemma.
"We are taking a more mechanistic approach, using medical devices and not involving chemical targeting. The nanoshells we use don't need to know where the cancer is," Andreas Melzer, director of the Institute for Medical Science and Technology (IMSaT) at UD, told Medical Device Daily.
UD is collaborating with InSightec (Tirat Carmel, Israel) and CapsuTech (Nazareth, Israel) on what's called the Nanoporation Project, intended to integrate MRI, focused ultrasound and photonics, for the delivery and activation of nanocapsules that carry high doses of chemotherapy to effectively destroy tumors.
The treatment starts with chemotherapy being encapsulated inside nanocapsules which are injected into a patient and remain harmless to the body until they are activated by a concentrated focused ultrasound blast.
"We use a system that's been developed by InSightec for high intensity focused ultrasound (HIFU), which can be focused inside the body," Melzer said. "Under controlled MRI, the focus spot can be placed on images taken from a patient showing a tumor. The benefits of using this are that MRI has a superior imaging of tumors and MRI has become good at temperature mapping. Each hot spot caused by HIFUs achieves 56 degrees Celsius and all the cancerous cells are destroyed.
"Our approach – called MRI-guided Focused Ultrasound (MRgFUS) – to use the system is to actuate nano-sized nanocapsules which carry potent and toxic chemotherapy agents released from the nanoshells under the influence of ultrasound," Melzer said, adding. "We avoid the side effects of chemotherapy this way."
One of the biggest advantages of nanoporation is that it would not only treat the obvious tumor, but also the tiniest cancer cells in the area that aren't yet visible.
Because of this particular benefit of the therapy, the team has chosen to develop nanoporation with immediate indications for colon, prostate and breast cancers.
"Breast cancer is one of the most interesting, because in breast, micro-metastasized cells can't be visualized," he said. "This whole area around the tumor would be subject to treatment so that the breast can be preserved. Our approach seems to have the best application with breast cancer. Prostate cancer is a complex cancer with various treatment problems. In thermo ablation therapy or surgery important nerves are destroyed. Our targeted approach may be very appropriate for this too."
This would be ideal for colon cancer, too, because when it metastasizes, it typically grows to the liver, which cannot be ablated. Nanoporation would help to stem this spread of the micro-metastasized cells.
InSightec's MRgFUS system will be combined with CapsuTech's nanocapsules.
"Our approach is to take these drugs, cover then with nanoshells – that's the CapsuTech part – so that the drugs are inert and don't cause side effects," Melzer said. "They work only when the ultrasound targets them and they are then released. We'll take previously FDA-approved drugs and combine with a drug carrier and then it's a medical device used as a drug delivery system similar to drug eluting stents."
Melzer's group has been working on the project already for four years in cell cultures with human cell lines from colon, prostate and breast cancer.
The four-year project will involve first proving that the drug release from nanoshells can occur on command. Melzer expects that to achieve this stage within the next 1.5 years. After that, they'll start experiments in small animals.
One of the key points is to discover just how hot the focused ultrasound needs to be to release the drugs, but to avoid destruction of cells and the drug.
Sandy Cochran, deputy director/team leader (Medical Ultrasound), IMSaT, said the drug release will likely occur at lower temperatures than currently used in HIFU technologies so that the drug isn't destroyed along with avoiding burns or tissue damage around the site.
The group will also tap into photonics technologies, manipulating light, as part of their research.
"Optical elements of light are used to trap nanoparticles," Cochran said. "We can localize a single nanoshell and load the drug under microscopes to study with high speed camera how the effects of ultrasound work. So photonics will be engaged for research use only, to study and understand the process."
Even though the chemotherapeutics, like cisplatin, will be delivered in such a targeted manner, it remains to be seen what, if any, side effects patients will experience after the job is done and until the drugs and remaining nanocapsules clear the body.
"That's a very difficult question," Melzer said. "We're still studying how nano-sized drugs are eliminated. Obviously we wouldn't go over the conventional dosages of the drug. But these are the same questions that surrounded the development of drug eluting stents. Is the concentration around the stent higher than if used systemically? We intend to prove it's the same concentration."
The project has been funded for four years through the European Union's Framework 7 program with a €2 million grant. The two companies involved are contributing technology and resources, but have not made direct financial investments.