Nanocapsules overcome chemotherapy resistance

One of the most challenging situations that oncologists face is when chemotherapy fails to slow down or stop the growth of cancer. This phenomenon, called multidrug resistance, is the result of several simultaneous biochemical processes that scientists do not fully understand. New research from UNC-Chapel Hill offers hope to cancer doctors and patients facing this heartbreaking situation.

The research, led by pharmaceutical scientist Russell Mumper, Ph.D, director of the UNC Center for Nanotechnology in Drug Delivery and member of the UNC Lineberger Comprehensive Cancer Center, uses nanotechnology to overcome multidrug resistance.  

Mumper’s team used an innovative formulation of lipid nanocapsules loaded with the anti-cancer drugs doxorubicin or paclitaxel to destroy cancer cells both in laboratory-based experiments and in a mouse model of ovarian tumors.  The nanocapsules inhibit a key protein that enables cancer cells to expel chemotherapy drugs, reducing the drug concentration within the cell and the drug’s overall effectiveness in killing cancer cells.

They found that the nanocapsules – sub-microscopic spherical gel capsules – loaded with the drugs resulted in a higher concentration of the drugs within the cell than use of either drug without the nanocapsule delivery system. The new paclitaxel nanocapsule formulation completely stopped the growth of multidrug resistant ovarian cancer tumors, whereas the commercially available drug Taxol® was completely ineffective at stopping tumor growth in this group of mice.  The team has also shown that the nanocapsule formulation was able to reduce the tumor size in mice that had previously failed conventional Taxol therapy.

Their findings, which are currently online and will appear in the May 1 issue of the journal Cancer Research, are the first to demonstrate this effect.

“We have several theories about why this works, and they all may play a role. In this study, we were able to show that the presence of the nanocapsules inhibits the key protein involved in pumping the chemotherapy drugs out of the cells – possibly by slowing down the cell’s metabolism and making the cancer cells much more susceptible to the otherwise potent anti-cancer drugs,” said Mumper, who is a professor in the UNC Eshelman School of Pharmacy.

“This work is important and technically sophisticated.  It delivers a two-pronged attack on drug resistant cancer cells, delivering a potent drug and preventing resistance to that drug,” said cancer center director Shelton Earp, M.D.
 
“This new approach should help to overcome resistance to therapy, a problem that plagues our patients with advanced disease.  We are eager to see how it works in additional preclinical testing,” he added.

The research was funded by a grant from the National Cancer Institute, part of the National Institutes of Health.