February 28, 2013
From Spheres To Rods, Reshaping Chemotherapy Drugs May Make Them Far More Effective
Watch the video "Chemotherapy Drugs Getting Better at Targeting Cancer Cells"
redOrbit Staff & Wire Reports - Your Universe OnlineChanging the shape of chemotherapy drug nanoparticles to make them rod-shaped rather than spherical can enhance their effectiveness in targeting and treating breast cancer cells by as much as 10,000-fold, according to new research from bioengineers at the University of California, Santa Barbara (UCSB).
As part of the research, a team led by Samir Mitragotri, a professor of chemical engineering and director of the UCSB´s Center for Bioengineering, discovered that their nanoparticle shape-changing method could make chemotherapy more efficient and effective. By simply making the drugs rod-shaped, they were more likely to correctly target cancer cells and less likely to accumulate in a person´s liver, lungs and spleen.
“What we have done here is to take the antibodies and combine them with chemotherapy drugs and show that they can be very effective,” explained Mitragotri. “Now when people make nanoparticles, they usually talk about spheres. They make a nice spherical, round particle, and that´s good. But what we found out, and what we hypothesize, is that if you make the particles into a different shape — in our case, rod — they work much better.”
In order to create these enhanced chemotherapy drugs, Mitragotri, post-doctoral researchers Sutapa Barua and Jin-Wook Yoo, and former graduate student Poornima Kolhar (all of whom are affiliated with UCSB) took a standard chemotherapy drug and reworked it in a laboratory to create rod-shaped nanoparticles. They then coated those nanoparticles with trastuzumab, an antibody that interferes with a specific type of protein receptor and is used to treat breast cancer.
According to Barua, tratsuzumab binds to the surface of a cancer cell with those receptor proteins, which she identifies as Human Epidermal Growth Factor Receptor 2 (HER2). When the antibody bonds to those receptors, it stops the activity of the HER2 proteins, which in turn stops the growth of the cancer cell. Normally, tratsuzumab´s efficiency level is low, but using rod-shaped nanoparticles can increase its efficiency by up to 50 percent when using just one microgram per milliliter of the antibody´s solution.
“This unique approach of engineering shapes of anti-cancer drugs and combining them with antibodies represents new direction in chemotherapy,” Mitragotri said Wednesday in a statement. “We were inspired to look at the shape as a key parameter by natural objects. In nature, all key particles such as viruses, bacteria, red blood cells, platelets are non-spherical. Their shape plays a key role in their function.”
The team´s findings have been published in a recent edition of the journal Proceedings of the National Academy of Sciences (PNAS), and their work was supported by Genentech, the UC Discovery Program, and the Daryl and Marguerite Errett Discovery Award in Biomedical Research.