DNA-Constructed Nanoparticles Safely Target Tumors

A team of Canadian researchers has discovered a way to assemble “building blocks” of gold nanoparticles as the vehicle to deliver cancer medications or cancer-identifying markers directly into cancerous tumors.

The study, led by Prof. Warren Chan, of University of Institute of Biomaterials & Biomedical Engineering (IBBME; ON, Canada) and the Donnelly Center for Cellular & Biomolecular Research, was published February 2014 in the journal Nature Nanotechnology.

“To get materials into a tumor they need to be a certain size,” explained Prof. Chan. “Tumors are characterized by leaky vessels with holes roughly 50–500 nm in size, depending on the tumor type and stage. The goal is to deliver particles small enough to get through the holes and ‘hang out’ in the tumor’s space for the particles to treat or image the cancer. If particle is too large, it can’t get in, but if the particle is too small, it leaves the tumor very quickly.”

Prof. 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, like putting LEGO blocks together,” said Leo Chou, a fifth-year PhD, student at IBBME and first author of the paper. “The major advantage of this design strategy is that it is highly modular, which allows you to ‘swap’ components in and out,” he said. “This makes it very easy to create systems with multiple functions, or screen a large library of nanostructures for desirable biological behaviors."

The long-term risk of toxicity from particles that linger in the body, however, has been a serious hurdle to nanomedical research. “Imagine you’re a cancer patient in your 30s,” said Prof. Chan. “And you’ve had multiple injections of these metal particles. By the time you’re in your mid-40s these are likely to be retained in your system and could potentially cause other problems.”

Although DNA is flexible, and over time, the body’s natural enzymes cause the DNA to degrade, and the grouping breaks apart. The body then eliminates the smaller particles safely and easily. But while the researchers are excited about this breakthrough, Prof. Chan stressed that a lot more details need to be determined. “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 nanoconfigurations for cancer applications.”

Related Links:
University of Toronto’s Institute of Biomaterials & Biomedical Engineering