Two Canadian engineers are taking nanotechnology to new levels in the fight against cancer. Warren Chan at the University of Toronto's biomedical engineering department uses DNA sequencing to change the shape, size and chemistry of modular nanoparticles to target cancer in specific organs. Meanwhile, his counterpart, the director of the Polytechnique Montréal's Nanorobotics Laboratory, Sylvain Martel, has developed bacterial nanorobotic agents, which target powerful chemotherapeutic drugs at fast-growing cancer tumors.

"We don't go through the body's circulatory system," Martel told BioWorld Today. "We go directly from point A to point B, guiding those bacterial agents using a magnetic field directly to the tumor. Once there, these bacteria deliver a high percentage of drug molecules to the cancer, but without systemic exposure."

Martel's 3-D magnetic platform exploits two natural systems within the body: magnetic iron oxide nanoparticles called nanoliposomes, which draw up to 100 million bacteria to the tumor site via an induced magnetic field, and the bacteria's natural sensors, which locate areas where cancer cells consume high levels of oxygen and dispense chemotherapeutic drugs to attack the cancer.

That involves two challenges, said Martel. First, pressure within a tumor inhibits flow so that the drug-carrying molecules can't diffuse or go very deep. Second, tumors typically are not homogeneous in regions of the tumor where cancer cells grow rapidly, i.e. the hypoxic region. Combining a low magnetic field with the 70 iron oxide nanoparticles aboard the bacteria creates, in effect, a microscopic compass needle that draws the bacteria to the tumor.

Once the nanoliposomes are inside the tumor, lab technicians turn off the magnetic field, and the bacteria switch to their own natural oxygen sensors, which guide them to the hypoxic area.

"When cancer cells duplicate, they consume high levels of oxygen, which reduce the oxygen level in this region to around 0.5 percent," said Martel. "And that's what these particular types of bacteria seek."

Once they arrive, chemotherapeutic drugs attached to the bacteria attack and kill the cancer cells.

THE SHAPE-SHIFTING EFFECT

Similarly, Chan's research at the University of Toronto involves targeting nanoparticles to tumor sites where chemotherapeutic drugs are dispensed to kill cancer cells. However, the shape, size and molecular chemistry of different organs vary, so that the ease with which nanoparticles enter those organs to combat the cancer tumor also varies.

"What we've shown is that one out of 100 drug-carrying nanoparticles actually go to the tumor site," Chan told BioWorld Today. "The other 99 are trapped inside other different organic tissues." Following that discovery, Chan's next step was to understand why that happens and "to use that information to engineer particles which avoid that entrapment."

Chan designed a system using DNA sequencing to tailor those modular nanoparticles to the molecular chemistry of particular organs, i.e. changing their size and shape so that the nanoparticles can attack the cancer tumor but not other organs.

"We're trying to mimic behaviors of certain biological molecules in the body," Chan said, "but by mimicking these to create the best targeting agent that will have the highest therapeutic specificity."

That agent is then injected into the bloodstream where the nanoparticles circulate. Chan's design calls for a ligand molecule placed on the nanoparticle surface, which recognizes unique sets of receptors on cancer cells that enable them to survive. At that point, the nanoparticles enter the tumor through small openings or compression channels that emerge in the tumor as it rapidly grows. The drug accompanying the nanoparticle then attacks and kills the cancer cells.

TWO BETTER THAN ONE?

With both technologies in mind, an obvious question emerges: Might Martel's magnetic field be used to more directly target Chan's shape-shifting nanoparticles to the cancer site?

"Sure," said Martel. "That's the goal. We want a general transport system, and we're hoping other research groups work with us to see what works the best."

Chan agreed. "I think in the longer term his system may allow it to localize a higher concentration of drug-carrying nanoparticles and once it's located at the tumor site you can maneuver it to only target the cells there."

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