Combining Two Drugs in One Nanoparticle Overcomes Multidrug Resistance
Cancer cells, like bacteria, can develop resistance to drug therapy. In fact, research suggests strongly that multidrug-resistant cancer cells that remain alive after chemotherapy are responsible for the reappearance of tumors and the poor prognosis for patients whose cancer recurs. One new approach that shows promise in overcoming such multidrug resistance is to combine two different anticancer agents in one nanoscale construct, providing a one-two punch that can prove lethal to such resistant cells. This work appears in the journal Molecular Pharmaceutics.
Mansoor Amiji, Ph.D., principal investigator of the National Cancer Institute-funded Nanotherapeutic Strategy for Multidrug Resistant Tumors Platform Partnership at Northeastern University, and postdoctoral fellow Srinivas Ganta, Ph.D., created a nanoemulsion entrapping both paclitaxel and curcumin. The former compound is a widely used anticancer agent, whereas the latter comes from the spice tumeric and has been shown to inhibit several cancer-related processes.
The investigators prepared their nanoformulation by mixing the two drugs with flaxseed oil, the emulsifier lecithin from egg yolks, and the biocompatible polymer polyethylene glycol. To help track this nanoformulation, the investigators also added a fluorescent dye to the mixture. Ultrasonification for 10 minutes produced stable, nanosize droplets that were readily taken up by tumor cells grown in culture. In addition, the nanoformulation had significant anticancer activity that surpassed that of either of the two drugs administered together or separately, particularly in multidrug-resistant cells. Biochemical assays showed that the curcumin component inhibited P-glycoprotein, which tumor cells use to excrete anticancer agents and protect themselves from the effects of those agents. Both drugs also had the effect of triggering apoptosis in the treated cells.
This work, which was detailed in the paper “Coadministration of paclitaxel and curcumin in nanoemulsion formulations to overcome multidrug resistance in tumor cells,” was supported by the NCI Alliance for Nanotechnology in Cancer, a comprehensive initiative designed to accelerate the application of nanotechnology to the prevention, diagnosis, and treatment of cancer. An abstract is available at the journal’s Web site.