茄子直播

鈥淲e鈥檙e making shape-changing nanoparticles,鈥 Professor Warren Chan says. 鈥淭hey鈥檙e a series of building blocks, kind of like a LEGO set.鈥 (photo by NSERC)

Engineering nanoparticles that can change their shape to deliver cancer drugs to tumours

Attached to strands of DNA, they change shape, size and chemistry to access diseased tissue, like a key fitting into a lock

Chemotherapy isn鈥檛 supposed to make your hair fall out 鈥 it鈥檚 supposed to kill cancer cells. A new molecular delivery system created at 茄子直播 Engineering could help ensure that chemotherapy drugs get to their target while minimizing collateral damage. 

Many cancer drugs target fast-growing cells. Injected into a patient, they swirl around in the bloodstream acting on fast-growing cells wherever they find them. That includes tumours, but unfortunately also hair follicles, the lining of your digestive system, and your skin.

The University of Toronto's Professor Warren Chan has spent the last decade figuring out how to deliver chemotherapy drugs into tumours 鈥 and nowhere else. Now his lab has designed a set of nanoparticles attached to strands of DNA that can change shape to gain access to diseased tissue. Their research will be published on Feb. 19.

鈥淵our body is basically a series of compartments,鈥 says Chan. 鈥淭hink of it as a giant house with rooms inside. We鈥檙e trying to figure out how to get something that鈥檚 outside, into one specific room. One has to develop a map and a system that can move through the house where each path to the final room may have different restrictions such as height and width.鈥

One thing we know about cancer: no two tumours are identical. Early-stage breast cancer, for example, may react differently to a given treatment than pancreatic cancer, or even breast cancer at a more advanced stage. Which particles can get inside which tumours depends on multiple factors such as the particle鈥檚 size, shape and surface chemistry.

Chan and his research group have studied how these factors dictate the delivery of small molecules and nanotechnologies to tumours, and have now designed a targeted molecular delivery system that uses modular nanoparticles whose shape, size and chemistry can be altered by the presence of specific DNA sequences.

鈥淲e鈥檙e making shape-changing nanoparticles,鈥 says Chan. 鈥淭hey鈥檙e a series of building blocks, kind of like a LEGO set.鈥 The component pieces can be built into many shapes, with binding sites exposed or hidden. They are designed to respond to biological molecules by changing shape, like a key fitting into a lock. 

These shape-shifters are made of tiny chunks of metal with strands of DNA attached to them. Chan envisions that the nanoparticles will float around harmlessly in the blood stream, until a DNA strand binds to a sequence of DNA known to be a marker for cancer. When this happens, the particle changes shape, then carries out its function: it can target the cancer cells, expose a drug molecule to the cancerous cell, tag the cancerous cells with a signal molecule, or whatever task Chan鈥檚 team has designed the nanoparticle to carry out.

Their work was published this week in two key studies in the Proceedings of the National Academy of Sciences and the leading journal Science.

鈥淲e were inspired by the ability of proteins to alter their conformation 鈥 they somehow figure out how to alleviate all these delivery issues inside the body,鈥 says Chan. 鈥淯sing this idea, we thought, 鈥楥an we engineer a nanoparticle to function like a protein, but one that can be programmed outside the body with medical capabilities?鈥欌

Applying nanotechnology and materials science to medicine, and particularly to targeted drug delivery, is still a relatively new concept, but one Chan sees as full of promise. The real problem is how to deliver enough of the nanoparticles directly to the cancer to produce an effective treatment. 

鈥淗ere鈥檚 how we look at these problems: it鈥檚 like you鈥檙e going to Vancouver from Toronto, but no one tells you how to get there, no one gives you a map, or a plane ticket, or a car 鈥 that鈥檚 where we are in this field,鈥 he says. 鈥淭he idea of targeting drugs to tumours is like figuring out how to go to Vancouver. It鈥檚 a simple concept, but to get there isn鈥檛 simple if not enough information is provided.鈥

鈥淲e鈥檝e only scratched the surface of how nanotechnology 鈥榙elivery鈥 works in the body, so now we鈥檙e continuing to explore different details of why and how tumours and other organs allow or block certain things from getting in,鈥 adds Chan.

He and his group plan to apply the delivery system they鈥檝e designed toward personalized nanomedicine 鈥 further tailoring their particles to deliver drugs to your precise type of tumour, and nowhere else.

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