Colorectal cancer is one of the leading causes of cancer deaths worldwide. Tumour progression involves two main mechanisms: the growth of blood vessels and the growth of cancer cells. Although new anticancer agents have been developed in recent years, administering a single anticancer drug – either one that acts on blood vessel growth (antiangiogenic) or one that stops cancer cells from proliferating (antimitotic) – often proves inefficient. Indeed, many patients can even become resistant to the drug.

Nanotechnology is promising for the field of drug delivery and in the case of colon cancer, combining antivascular and cytotoxic agents in a single nanoplatform might help improve tumour treatments. The problem is that, when delivered as free agents, antivascular compounds can “shut down” tumour blood vessels – something that prevents the subsequently administered cytotoxic drug from penetrating the tumour site.

Two agents in one nanocomposite

Now, a team led by Patrick Couvreur of the University Paris-Sud has gone a long way in overcoming this problem and has managed to incorporate both agents in one nanocomposite. The researchers have constructed nanoassemblies containing both isocombrestatine (isoCA-4), a drug that disrupts blood vessel growth, and the anticancer agent squalenoyl gemcitabine (SQgem).

So how does the drug combination work? “IsoCA-4 is completely insoluble in water,” explains Couvreur. “Therefore, this compound dissolves in the squalenoylated gemcitabine – which is a fatty structure. Thanks to this strategy, the amounts of gemcitabine and SQ-gem contained in each dose can be much higher than is possible if the two drugs were administered on their own,” he told

The team has already tested its treatment technique on mice bearing human colon cancer cells and found that the nanocomposites can regress tumours by as much as 93%. The double treatment also appears to be better tolerated by the mice than when the drugs are administered separately.

The researchers, who report their work in ACS Nano, say that they would now like to look at applying their multidrug technique to diseases other than cancer.

Further reading

Polymer capsules target cancer cells (Feb 2012)
Nanocomposites deliver drugs (Feb 2011)