DNA binding creates potentially nontoxic tumor-targeting structures
L.Y.T. Chou et al/Nature Nanotech.
Eat your heart out Amazon. Packaging made of DNA-strapped nanoparticles could deliver cancer drugs directly to a tumor’s doorstep, then quickly break down and see itself to the curb.
Researchers have used nanoparticle-based parcels to carry drugs to tumors before. But the new shipping system, which was tested in mice, is the first to specify an exit strategy for the nanoparticles, which are often made of toxic metals that can accumulate in healthy tissues. The results appear January 26 in Nature Nanotechnology.
Biomedical engineer Warren Chan of the University of Toronto and colleagues created gold nanoparticles that can link together like Tinkertoys to build bigger, more complex structures. The particles’ linkers are single strands of DNA chemically fused to each gold nanoparticle. The dangling DNA strings can connect with complementary DNA on other nanoparticles to create nearly endless combinations of particles.
“This is a beautiful design,” says biomedical engineer Zhen Gu of the University of North Carolina at Chapel Hill. The customizable system is simple and adjustable for different drugs and tumor types, he says.
By tweaking the size and DNA code of the links, Chan and his team created nanoformations that could bind a cancer drug called doxorubicin and others that go directly to tumors in mice. The DNA connectors carried the drug, and the size of the assemblies — around 100 nanometers across — allowed the structures to squeeze through tumors’ unique pores without lingering in most healthy tissues.
What happens next is the real trick. Immune cells called macrophages, which gobble up foreign materials and remove them from the body, take up the nanostructures and degrade their DNA buttressing. The structures release their gold particles, which are small enough to float out of cells and leave the mouse body via urine.
“It is a pretty unique approach,” says nanomedicine researcher Willem Mulder of the Icahn School of Medicine at Mount Sinai in New York City. But, he adds, it will need more validation and tweaking before testing on people.
L.Y.T. Chou, K. Zagorovsky and W.C.W. Chan. DNA assembly of nanoparticle superstructures for controlled biological delivery and elimination. Nature Nanotechnology. Published online January 26, 2014. doi: 10.1038/nnano.2013.309.
A. Yeager. Nanoparticle injection blocks breast cancer growth in mice. Science News Online, January 3, 2014.
J. Raloff. Nanoparticles' indirect threat to DNA. Science News Online, November 5, 2009.