Feb 10, 2014
Nanoparticle superstructures break down in the body
Inorganic nanoparticles can be ideal drug-delivery vehicles and be used to target cancer cells in vivo. However, these particles can build up in the body and potentially become toxic. Researchers at the University of Toronto in Canada may now have come up with a way to overcome this problem – by using DNA to build superstructures of gold nanoparticles that degrade into their constituent building blocks once their job has been done. The nanoparticles then safely clear from the body via natural processes.
Tumour-targeting nanoparticles need to be sufficiently large (up to 100 nm) so that they can efficiently travel to a tumour site and remain there long enough to give up their drug payload. However, the downside is that these big particles can also end up lingering in the body a long time. And because they do not biodegrade, they can build up in organs and tissue, possibly becoming toxic.
A team led by Warren Chan has now used DNA to organize nanoparticles less than 6 nm in diameter into larger superstructures that can safely carry drugs to tumour sites, but which then break down into their sub-structures so that they are eliminated via the kidneys in urine. 6 nm is the minimum diameter that can be removed through the kidneys in this way.
Core and satellite builds up superstructure
In their experiments, the researchers used gold nanoparticles that they coated with single-stranded DNA. They then added a second batch of gold nanoparticles coated with a different single-stranded DNA sequence so that the first batch (or “core”) of gold nanoparticles linked to the second (the “satellite”). “This process can be continued to build up multiple layers of nanoparticles, and this is one way to increase the size of our superstructure,” explained Chan.
“Our strategy is great for drug delivery because we can build the superstructure up to any size so that it is optimally taken up by cancer cells, but once it has released its cargo it can break down into its constituent building blocks and be easily eliminated from the body,” he told nanotechweb.org.
The researchers have shown that the method works in mice with tumours, injected with the superstructures. Fluorescence imaging revealed that the large particle assemblies accumulated at a cancerous site (see figure) and urine samples collected for up to 48 h post-injection were full of the smaller constituent structures.
Non-toxic and well tolerated
To make sure that the superstructures themselves were non-toxic, Chan’s team tested blood from the mice and analysed the animals’ major organs using techniques such as histology. “The results show that, although a large proportion of the superstructures also accumulated in the liver and spleen, they did not cause acute toxicity and were well tolerated by the animals at the doses employed in our experiments,” said Chan.
It is early days for us yet, however, and it should be a few years before we can begin clinical trials in the hospital using our protocol, he adds. “We have a lot of basic studies to undertake beforehand and although these studies will not be too challenging, they will be important because they will help us transfer the technology from mice to humans.”
The researchers detail their work in Nature Nanotechnology doi:10.1038/nnano.2013.309.
About the author
Belle Dumé is contributing editor at nanotechweb.org