New `one-two punch` system kills breast cancer tumour cells

Washington, Oct. 27 (ANI): MIT chemical engineers have designed nanoparticles that can carry the cancer drug doxorubicin, as well as short strands of RNA that can shut off one of the genes that breast cancer cells use to escape the drug.

Lead author of the paper is Jason Deng, a postdoc in Hammond's lab. Other authors are MIT graduate student Stephen Morton, junior Elana Ben-Akiva, and postdocs Erik Dreaden and Kevin Shopsowitz.

Triple-negative breast tumors lack the three most common breast cancer markers: estrogen receptor, progesterone receptor, and Her2. Scientists have developed treatments that target each of those markers, which have improved survival rates for those cancers.

Paula Hammond, the David H. Koch Professor in Engineering, a member of MIT's Koch Institute for Integrative Cancer Research, and leader of the research team, said that typically these personalized therapies have been much more effective than just dousing with a chemotherapy drug, because they're getting at the ways in which tumor cells operate.

She hopes that the new nanoparticles, which target a protein found on the surface of triple-negative breast cancer cells, will help to change that. The nanoparticles have three components: a core filled with doxorubicin, a coating of short interfering RNA (siRNA), and an outer layer that protects the particle from degradation in the bloodstream.

Doxorubicin, a drug that kills cells by damaging their DNA, is already used to treat breast cancer and other cancers, including lung, ovarian, and thyroid. The researchers based their nanoparticles on a Food and Drug Administration-approved form of the drug known as Doxil, which is packaged in a liposome, or fatty membrane.

To improve Doxil's effectiveness, Hammond's team wanted to combine it with another type of therapy known as RNA interference (RNAi), which uses very short strands of RNA to block the expression of specific genes inside a living cell.

The researchers used a technique called layer-by-layer assembly to coat the Doxil particles with one layer of siRNA mixed with a positively charged polymer that helps to stabilize the RNA. This layer contains up to 3,500 siRNA molecules, each targeted to block a gene that allows cancer cells to pump the drug molecules out of the cells.

The study has been published in the journal ACS Nano.

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