The future of medicine is very small

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Physician-sleuth

By Michelle Pucci

You’re ill. You visit a doctor who examines you, diagnoses you with a once deadly cancer, immediately offers some non-invasive treatment, and sends you home with a good prognosis, relatively free of pain and side effects.

It’s a scene straight out of Star Trek, but it might not be too far from reality.

“The concept is an old human-being dream, to have access to such treatment,” says Dr. Té Vuong, Associate Professor and Co-chair of McGill Radiation Oncology and Director of the Segal Cancer Centre’s Radiation Oncology facility at the Jewish General Hospital.

Vuong is one of several McGill cancer researchers working on a drug delivery system using nanotechnology to make cancer treatment more effective. The key: a strain of bacteria, orginally isolated from water collected from the Pettaquamscutt Estuary in Rhode Island.

Smaller than a red blood cell, these bacteria are being engineered to carry drugs into the core of tumours, or act as radiosensitizers by targeting oxygen-deprived cells and making them more sensitive to radiation.

At the helm of this project is Sylvain Martel, MEng, PhD, Director of École Polytechnique’s NanoRobotics Laboratory. A two-time McGill Engineering alumnus, his search for collaborators “to fill out the picture” led to his alma mater, where cancer research has long been a strength.

The interdisciplinary, interuniversity team is “not in the business of developing new drugs,” Martel explains.

Not drugs, but a drug delivery system

The “Rhode Island” bacteria are named magnetotactic for their magnetic properties. Put them inside a special platform developed by the NanoRobotics Laboratory, and the nanoparticles become supermagnetized. From there, they can navigate the bloodstream, with some guidance, and eventually make their way toward the tumour.

The bacteria are microaerophilic, surviving in environments where oxygen levels are 0.5%—far lower than the oxygen levels normally found in blood. Low oxygen levels, known as hypoxia, are found in solid tumours, and the lack of oxygen reduces the efficiency of radiation therapy. For the bacteria, though, those low levels can be an advantage.

When there’s no signal from the magnetic field, the bacteria use oxygen sensors to find the area with proper levels in order to survive.

Under the right conditions, left at room temperature, these bacteria grow, making them cheap to reproduce.

Once inside the human body, the bacteria have less than an hour to get to their destination before they die, which is still enough time for them to accomplish their mission.

The goal is to get drugs or radiosensitizers into the core of the tumour, instead of trying to siege from the outside using chemotherapy or radiation.

A cancer biologist and an oncologist walk into a lab…

“The project is very novel in the fact that we’re getting a whole big team of rather prominent people working together,” says Dr. Nicole Beauchemin, Professor, Rosalind and Morris Goodman Cancer Research Centre, departments of Biochemistry, Medicine and Oncology, McGill University.

Beauchemin, a cancer biologist who specializes in developing tumours in mice, says that using Vuong’s expertise as a colon and rectal cancer oncologist, the team was able to develop a model for the treatment of rectal cancer.

“On the mouse model it was just ‘Oh my god,'” says Beauchemin, who describes this interdisciplinary collaboration as one of the most satisfying experiences she has ever had as a scientist.

Learning to speak “engineer”

With specialists coming from various fields, researchers need to overcome communication challenges. Having biologists, surgeons and oncologists speaking different disciplinary “languages” can limit collaboration and growth, says Gerald Batist, MDCM’77, Director, Segal Cancer Centre, Jewish General Hospital; Director of the McGill Centre for Translational Research in Cancer; and Professor of Oncology. Throw in engineers and you add a whole other layer of difficulty.

“In any field, it’s really the future, being able see things from different perspectives,” he says. “It’s limited by language.”

Beauchemin says the interdisciplinary experience on this project has been positive for the students involved. It is an opportunity for them to learn how to explain the science behind their work in a way that the majority of people will understand—an important task of a medical education.

Particles that point to cancer

The first steps to better cancer treatment start with identifying the disease.

Over at the McGill University and Génome Québec Innovation Centre, Dr. David Juncker and his team are investigating cancer diagnostics and screening technologies in the Micro & Nano Bioengineering Lab.

One tool is a filtration technique to isolate cells that could be linked to cancer, based on size, but also based on molecular features. The initial work was done at the McGill Nanotools Microfab, a facility dedicated to developing micro- and nanotechnologies, says Juncker, a Canada Research Chair in Micro- and Nanobioengineering and Professor in Biomedical Engineering at McGill.

The microfabricated filters are engineered to catch circulating tumour cells, which could signal whether cancer has spread.

“The next step is to go to the clinic and try this setup with patient samples,” Juncker says.

Juncker’s lab is also developing microfluidics and microarrays, both of which are techniques using “lab-on-a chip” technologies that function like mini-laboratories, testing samples for particles that could point to cancer.

“What you need is to have technologies that are user-friendly and economically viable and also provide actionable information in the end,” Juncker says. “There’s still a big gap there.”

The goal is to use biomarker signatures with the new technologies in diagnostics for cancer patients. Using blood samples and microarrays—chips with dots that measure proteins—Juncker and his team are looking to identify breast cancer biomarkers, which are molecules released by tumours. These molecules are signs that cancer is present in the body.

The first cancer biomarker was discovered at McGill half a century ago, by Phil Gold, BSc, MDCM’61, MSc’61, PhD’65, and Samuel Freedman, BSc, MDCM’53, DipIntMed’58, DSc, and is still used widely today.

“What we are trying to do is make more markers so we can have a much more comprehensive idea,” Juncker says. “Like a fingerprint, you have many different parameters, so that fingerprint identifies something unique.”

Meanwhile, Dr. Joseph Matt Kinsella, Assistant Professor of Bioengineering at McGill, is using materials like bismuth to create nanoparticle compounds to track tumours and improve screening. The bismuth compounds act as a dye to appear in CT scans and x-rays. When combined with a peptide, a compound of amino acids, the nanoparticles can be labelled to target and bind with tumours, providing a new method for diagnosis.

If Kinsella’s team proves these materials can be used to avoid things like biopsies, the cancer screening process can be sped up, saving much of the clinical work.

From dorm to bloodstream

“I’ve been doing this for a long time,” says Thomas Chang, BSc, MDCM’61, PhD’65.

Chang was an undergraduate at McGill when he invented the first artificial cell. His work, begun in his Douglas Hall dorm room, eventually led to the creation of McGill’s Artificial Cells & Organs Research Centre.

“I told my classmate and professor, ‘I’m trying to make artificial cells,’ and they started laughing at me, saying, ‘You must be nuts.’

“The cells can be micro- or nano-sized, or soluble nanobiotechnological complexes made of a nano-thick synthetic membrane, encapsulating any biological material, from haemoglobin to adsorbents,” Chang explains.

With artificial cells, Chang has developed haemoperfusion techniques using activated charcoal, among other materials. The cylinder-shaped devices fit in the grip of a hand and can be fixed to the inside of an arm to remove toxins from blood by filtering it through artificial cells containing charcoal. The process—in use around the world—is faster and more effective than larger artificial kidney machines, he says.

Now Chang is working towards developing artificial cells that can be used in the place of blood.

Existing blood substitutes aren’t approved for use in North America, because there is a 3% chance of heart attack, but artificial blood cells are being used for patients with chronic anemia in South Africa, to eliminate the risk of transmitting HIV through contaminated blood.

New research by Chang will show that artificial blood cells are more effective than donor blood, after bioengineering the cells to contain equal if not more concentrations of blood-specific enzymes, eliminating the risk of cardiac side effects. Another advantage of this technology: it costs less than screening donor blood for viruses.

Dreaming of the day

“This project has a very special meaning to our whole team,” Vuong says about the collaboration with Martel. Everyone realizes that this is the kind of treatment from which they could one day benefit.

“I’ve had breast cancer, so I’ve had systemic chemotherapy, and I know what it does,” Beauchemin says.

Innovations in breast cancer surgery, from mastectomies to lumpectomies, have changed the outcomes for breast cancer patients significantly, says Batist. There are limits, however. Vuong cites colon and rectal cancer as an example. Even if patients don’t need a colostomy, and the bowel and sphincter are reconnected, quality of life is affected post-operation. Many patients, instead of going one to three times to the bathroom, might go five to ten times a day.

“We need to do something better,” says Vuong.

One nanometre at a time, we are.

What is nanotechnology? Microtechnology? Read:

 

 

 

 

 

 

 

 

 

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