Nanoparticles deliver punch to breast cancer

Triple negative breast cancer – an aggressive form of the disease – is very difficult to treat; researchers at MIT have developed a way to weaken tumour defences before striking them with chemotherapy.

Chemical engineers have designed nanoparticles containing cancer drug doxorubicin and short strands of RNA which can shut off one of the genes cancer cells use to evade the drug. This mechanism disables tumours’ defences, making them vulnerable to chemotherapy.

“It gives you, overall, a much more effective system at a lower dose, because you’re able to target these cells and ensure that each and every one of them receives the proper synergistic dosing of the two components,” said Paula Hammond, research leader.

The nanoparticles target CD44, a protein found in abundance on the surface of triple-negative breast cancer cells, and were able to shrink tumours in mice with cells of this type implanted under the skin.

The nanoparticles have three components - a core filled with doxorubicin, a coating of siRNA, and an outer layer that protects the particle from degradation in the bloodstream . They are based on Doxil, a form of doxorubicin packaged in a liposome, but to improve its effectiveness, the team combined it with RNA interference (RNAi), which uses very short strands of RNA to block the expression of specific genes inside a living cell.

Using layer-by-layer assembly, researchers coated Doxil particles with one layer of siRNA mixed with a positively charged polymer to stabilise the RNA. This layer contains up to 3,500 siRNA molecules, each targeted to block a gene that allows cancer cells to pump drug molecules out of the cells.

The particles are then coated in hyaluronic acid: “This stealth layer becomes a cushion of water surrounding the nanoparticle, which allows it to go through the bloodstream as if it were water,” Hammond said. “That makes it circulate much more effectively.”

In mice studies, the nanoparticles survived in the bloodstream longer than any RNA delivery particle previously tested, with a half-life of 28 hours, which gives them a much better chance of reaching the tumour. The nanoparticles were also engineered to release their payload quicker than doxorubicin once they reached the tumour.

The nanoparticles could be customised to treat other types of cancers by swapping the drug carried in the core, the siRNA target and the surface particles that target the tumour, say the researchers.

ACS Nano http://pubs.acs.org/journal/ancac3