Researchers from the Stanford University and the Massachusetts Institute of Technology (MIT) in the US have found a way to deliver platinum anticancer pro-drugs to tumours where the acidic environment causes them to be reduced and release the anticancer drug cisplatin.
The research, published in an early access article in the Journal of the American Chemical Society (JACS), shows that attaching pro-drugs to single walled carbon nanotubes (SWNT) significantly enhances the ability of these drugs to cross the cell wall.
While various previous studies have shown that carbon nanotubes can be used as nanoneedles approaches had typically used the tubes to encapsulate the drugs rather than 'carry' them.
"By combining the ability of platinum(IV) complexes that resist ligand substitution with the proven capacity of SWNTs to act as a longboat, shuttling smaller molecules across cell membranes, we have constructed SWNTs that effectively deliver a lethal dose of cisplatin upon reduction in the cell," write the authors.
Platinum anticancer drugs such as cisplatin often suffer a loss of activity in the body associated with poor circulation and delivery of the drug to the tumour as well as undergoing various deactivation mechanisms that render them useless.
The new technique uses a platinum(IV) pro-drug that can be easily attached to an amine-functionalised SWNT that can carry a payload of around 65 drug molecules per SWNT.
The prodrugs show very little cytotoxicity on their own and need to be reduced to platinum(II) before they show significant activity.
Interestingly, the acidic conditions that build up in and around cancerous growths make the reduction process much easier than when the prodrugs are in undiseased environments.
This may help reduce the number of side effects that are often exhibited by platinum anticancer drugs, especially cisplatin. These can include kidney damage, nerve damage, nausea, hearing loss and hair loss.
By co-tethering a fluorescent dye molecule to the Pt(IV) compounds the researchers were able to show that the fluorescent SWNTs were located inside small vesicles within the cells which supports previous evidence that suggests SWNTs are absorbed into cells by endocytosis.
Atomic absorption spectroscopy (AAS) of cells that had been incubated with SWNTs contained 6-8 times the amount of platinum than those incubated with the un-tethered pro-drug and twice as much as cells incubated with cisplatin.
The authors write: "by linking additional groups such as cancer-cell targeting groups to the platinated SWNTs as longboat passengers, it may be possible to achieve highly selective constructs for use in clinical trials."
