A team of researchers at the University of Toronto has discovered a method of assembling ‘building blocks’ of gold nanoparticles as the vehicle to deliver cancer medications, or cancer-identifying markers, directly into cancerous tumours.
The study, led by Professor Warren Chan of U of T’s Institute of Biomaterials & Biomedical Engineering (IBBME) and the Donnelly Centre for Cellular & Biomolecular Research, appears in an article in Nature Nanotechnology this week.
“To get materials into a tumour, they need to be a certain size,” explained Professor Chan. “Tumours are characterized by leaky vessels with holes roughly 50 – 500 nanometers in size, depending on the tumour type and stage. The goal is to deliver particles small enough to get through the holes and ‘hang out’ in the tumour’s space for the particles to treat or image the cancer.”
“If a particle is too large,” continued Chan, “it can’t get in, but if the particle is too small, it leaves the tumour very quickly.”
Professor Chan and his researchers solved this problem by creating modular structures ‘glued’ together with DNA.
“We’re using a molecular assembly model – taking pieces of materials that we can now fabricate accurately and organizing them into precise architectures. It’s like putting LEGO blocks together,” said Leo Chou, a PhD student at IBBME and first author of the paper. Chou was awarded a 2012-13 Canadian Breast Cancer Foundation Ontario Region Fellowship for his work with nanotechnology.
“The major advantage of this design strategy is that it is highly modular, which allows you to ‘swap’ components in and out,” said Chou. “This makes it very easy to create systems with multiple functions, or screen a large library of nanostructures for desirable biological behaviours.”
The long-term risk of toxicity from particles that remain in the body, however, has been a serious challenge to nanomedical research.
“Imagine you’re a cancer patient in your 30s, and you’ve had multiple injections of these metal particles,” said Professor Chan. “By the time you’re in your mid-40s, these are likely to be retained in your system and could potentially cause other problems.”
DNA, though, is flexible, and over time, the body’s natural enzymes cause the DNA to degrade, and the assemblage breaks apart. The body then eliminates the smaller particles safely and easily. While the researchers are excited about this breakthrough, Professor Chan cautioned that there is still more work to do.
“We need to understand how DNA design influences the stability of things, and how a lack of stability might be helpful or not,” he said. “The use of assembly to build complex and smart nanotechnology for cancer applications is still in the very primitive stage of development. Still, it is very exciting to be able to see and test the different nano-configurations for cancer applications.”
The project was funded by the Canadian Institutes of Health Research (CIHR), Natural Sciences and Engineering Research Council of Canada (NSERC), Canadian Breast Cancer Foundation (CBCF) and Canada Foundation for Innovation (CFI).