Altering the shape of chemotherapy drugs from spherical to rod-like has proven to increase the efficiency in targeting and treating breast cancer cells by nearly 10,000-fold.
Samir Mitragotri, a professor of chemical engineering and lead researcher, looked to nature for inspiration; viruses, bacteria, red blood cells and platelets all have non-spherical shapes.
“In general, non-spherical particles bind to their target more specifically compared to spherical particles,” said Mitragotri.
Biochemical engineers at UCSB discovered that the nanoparticle-shaped changing method could make chemotherapy more effectual because the rod-shaped drug will have a higher chance of correctly targeting the cancer cells rather than accumulating in the liver, lungs or spleen. “The major problem with the current anti-cancer drugs is to deliver the correct amount of the drugs to the right cells,” explained Sutapa Barua, a post-doctoral researcher in the Mitragotri lab.
After obtaining the desired rod-shape, researchers coated the surface of a polystyrene nanoparticle with trastuzumab, a monoclonal antibody that is selective for certain types of cancer cells. Trastuzumab then binds to the surface of the cancer cell body with receptor proteins Human Epidermal Growth Factor Receptor 2 (HER2).
Overexpression of HER2 is associated with aggressive types of breast cancer and thus has been used as a marker for the disease. The bound antibody stops the activity of HER2 that in turn stops the activity of the cancer cell. When the polystyrene nanorods were replaced with camptothecin nanorods, the specific uptake and lower non-specific uptake effects were enhanced: the camptothecin nanoparticles inhibited cell growth a 1,000-fold lower dose than that required for comparable growth inhibition with trastuzumab alone.
Antibodies are used with a variety of applications, including in vitro diagnostics of diseases such as infections. However, its effectiveness is dependent on the actual specificity of the antibody. Mitragotri’s research shows that putting the antibodies on the surface of rod-shaped nanoparticles will enhance both its specificity and avidity. Altering the shape of anti-cancer drugs and linking them with antibodies is a step in a new direction for chemotherapy.
Monoclonal antibodies, such as trastuzumab, mimic the endogenous antibodies; when it attaches to a cancer cell, it makes the cancer cell detectable to the immune system.
“Our findings will open up new opportunities in terms of making particles very selective and more effective against a variety of diseases, not just cancer but any other target,” said Mitragotri. The observations found are, in fact, quite general. Because all applications, including therapeutics and imaging, rely on binding of a targeting ligand to a cell, they will benefit from the rod-shaped particle.
A version of this article appeared on page 5 of April 2nd, 2013′s print edition of the Nexus