Researchers within the Pratt School of Engineering and the Duke Cancer Institute have designed a new nanoparticle--molecules tiny even by microscopic standards--that may offer the key to improved treatments for a variety of cancers. Ashutosh Chilkoti, professor of Biomedical Engineering and other Duke faculty in the Medical School and DCI found that their nanoparticles beat the current “gold standard” molecule used to deliver treatment for breast and prostate cancer. Their findings will be published in a coming issue of Nature Communication.
They used these nanoparticles to make paclitaxel, a commonly used cancer drug, more soluble and to last longer in the body upon injection. “Paclitaxel has many benefits, but the problem is it’s very hydrophobic, or unable to dissolve in water. It’s also a small molecule so its cleared rapidly cleared from the body, which severely limits its effectiveness”, lead author Jayanta Bhattacharyya said. Chilkoti’s team used their nanoparticles to package paclitaxel into a fully water soluble and long circulating format.
They then tested the effectiveness of their paclitaxel nanoparticles in mice with aggressive forms of prostate and breast cancer, comparing the results of this treatment to mice treated with Abraxane, the clinical gold standard for Paclitaxel delivery. Abraxane is made of Paclitaxel mixed with albumin —the most prevalent protein in blood— and reconstituted into nanoparticles. “Abraxane has many benefits for cancer treatment, but the problem is the drug is physically bound to human serum albumin, and these nanoparticles are not stable in blood and are nonspecifically absorbed by different tissues”, Bhattacharyya said.
The results were stunning. While cancer growth continued mice treated with Abraxane, most of the mice treated with the Duke nanoparticles experienced near-complete regression of their tumors. All of the mice with prostate cancer, and three-fourths the mice with breast cancer who received this new nanoparticle survived the full length of the experiment--weeks longer than any of the mice receiving the treatment with Abraxane.
“These results are extremely promising for two reasons,” said Ashutosh Chilkoti, PhD, leader of the Chilkoti Group at Duke Biomedical Engineering and a co-author in the study. “First, in a head-to-head contest Duke nanoparticles beat out a current FDA-approved gold standard for cancer therapy. Second, this methodology can be used to package any drug and make it water soluble.” This versatility could allow the nanoparticle formulation to improve treatment for a variety of cancers.
“Our next step is to explore ways to move this into the clinic, working with clinicians in the DCI,” Chilkoti said. “We also want expand upon the range of drugs whose effectiveness could be improved by this technology – many of the next generation cancer drugs are, like Paclitaxel, quite hydrophobic, so this technology should prove useful for the many new drugs coming out of the clinical pipeline.”
For more on nanoparticles, visit Pratt School of Engineering.
photo caption: Ashutosh Chilkoti, PhD, and Jayanta Bhattacharyya , PhD, observe a 96-well plate to quantify the elastin-like polypeptide (ELP) present in a solution.