DNA-built nanoparticles target cancer tumors, deal with toxicity

January 29, 2014

Design of nanoparticle superstructures using DNA assembly. Individual nanoparticles (yellow and red spheres) were coated with thiolated, single-stranded DNA and then assembled using linker DNAs containing complementary sequence regions. Nanoparticles located on the surface of superstructures were coated with additional ligands (for example, PEG, illustrated as blue clouds) to control superstructure interactions with cells and tissues. (Credit: LeoY.T.Chou et al./Nature Nanotechnology)

University of Toronto researchers have discovered a method of assembling building blocks of gold nanoparticles as the vehicle to deliver cancer medications or cancer-identifying markers directly into cancerous tumors while addressing the long-term risk of toxicity from particles that remain in the body.

“To get materials into a tumor they need to be a certain size,” explained Professor Warren Chan. “Tumors are characterized by leaky vessels with holes roughly 50–500 nanometers 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.”

Chan and his researchers solved this problem by creating modular structures glued together with DNA.

Dealing with toxic nanoparticles

But the research also focused on long-term toxicity. “Imagine you’re a cancer patient in your 30s,” said 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.”

DNA, though, is flexible, and over time, the body’s natural enzymes cause the DNA to degrade, and the assemblage breaks apart, he explained. The body then eliminates the smaller particles safely and easily.

However, Chan cautioned that the use of assembly to build complex and smart nanotechnology for cancer applications is still in the very primitive stage of development. “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 project was funded by the Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, Canadian Breast Cancer Foundation and Canada Foundation for Innovation.

Abstract of Nature Nanotechnology paper

The assembly of nanomaterials using DNA can produce complex nanostructures, but the biological applications of these structures remain unexplored. Here, we describe the use of DNA to control the biological delivery and elimination of inorganic nanoparticles by organizing them into colloidal superstructures. The individual nanoparticles serve as building blocks, whose size, surface chemistry and assembly architecture dictate the overall superstructure design. These superstructures interact with cells and tissues as a function of their design, but subsequently degrade into building blocks that can escape biological sequestration. We demonstrate that this strategy reduces nanoparticle retention by macrophages and improves their in vivo tumour accumulation and whole-body elimination. Superstructures can be further functionalized to carry and protect imaging or therapeutic agents against enzymatic degradation. These results suggest a different strategy to engineer nanostructure interactions with biological systems and highlight new directions in the design of biodegradable and multifunctional nanomedicine.