In the past, Nucleoside analogs like gemcitabine and cytarabine were merely considered to be powerful anti-cancer agents but a simple chemical modification can make them even more valuable in the treatment of many forms of cancer.
A research team that was headed by Patrick Couvreur, Ph.D., at the CNRS in Châtenay-Malabry, France, suggested that the new technique seems to work with almost all kinds of nucleoside analogs. Furthermore, it also has the net effect of enhancing the pharmacological behavior of compounds belonging to this class.
From News-Medical.Net:
A research team headed by Patrick Couvreur, Ph.D., at the CNRS in Châtenay-Malabry, France, found that attaching the molecule squalene to any one of several nucleoside analogs triggered a self-assembly process that creates nanoparticles that are stable in biological fluids. Squalene is a naturally occurring, water-insoluble compound involved in synthesizing steroid hormones. Linking this molecule to a water-soluble nucleoside analog causes the resulting conjugates to form a core-shell nanostructure, with the nucleoside analogs creating an outer layer that shields the squalene portion from the surrounding aqueous environment.
Tests using cultured tumor cells showed that a squalene-gemcitabine conjugate was up to eight times more potent as an anticancer agent compared to unmodified gemcitabine. In addition, these in vitro studies showed that the squalene-gemcitabine conjugate was able to kill cells that had developed resistance to gemcitabine. The researchers attribute the improved anticancer activity, in both normal and resistant cells, to the fact that the conjugate is poorly metabolized by the enzymes that normally detoxify nucleoside analogs.
Based on these promising results, the investigators then assessed anticancer activity of squalene-modified gemcitabine in both mouse and rat models of human leukemia. In each case, 40 percent of the animals treated with the squalene-gemcitabine conjugate survived for at least 100 days after treatment. In contrast, control animals that received a placebo or unmodified gemcitabine all died from cancer within 60 days.
In short, it was concluded that squalene-gemcitabine conjugate was potent by as much as eight times when compared to unmodified gemcitabine for treating varying forms of cancer.
