Multi-walled carbon nanotubes complement the anti-tumoral effect of 5-Fluorouracil

Abstract

Multiple-drug resistance in human cancer is a major problem. To circumvent this issue, clinicians combine several drugs. However, this strategy could backfire resulting in more toxic or ineffective treatments. Carbon nanotubes (CNTs), and particularly multi-walled nanotubes (MWCNTs), display intrinsic properties against cancer interfering with microtubule dynamics and triggering anti-proliferative, anti-migratory and cytotoxic effects in vitro that result in tumor growth inhibition in vivo . Remarkably, these effects are maintained in tumors resistant to traditional microtubule-binding chemotherapies such as Taxol ® . In the view of these properties, we investigate the use of MWCNTs in the development of active-by-design nanocarriers, attempting to enhance the effect of broadly-used chemotherapies. We compare the cytotoxic and the anti-tumoral effect of 5-Fluorouracil (5-FU) -an antimetabolite treatment of various forms of cancer- with that of the drug physisorbed onto MWCNTs. Our results demonstrate how the total effect of the drug 5-FU is remarkably improved (50% more effective) when delivered intratumorally coupled to MWCNTs both in vitro and in vivo in solid tumoral models. Our results demonstrate how using MWCNTs as anti-cancer drug delivery platforms is a promising approach to boost the efficacy of traditional chemotherapies, while considerably reducing the chances of resistance in cancer cells.

Microtubule cytoskeleton-disrupting activity of MWCNTs: applications in cancer treatment

“…Indeed, some studies demonstrate that CNTs can significantly boost the antitumoral effect of taxol®, boosting its cytotoxic effects, preventing and overcoming resistance to this drug [ 32 , 67 , 68 ]. More interestingly, MWCNTs have also been shown to boost the effect of other antitumoral drugs such as 5-fluorouracil [ 11 ] or doxorubicin [ 69 , 70 ] that are not catalogued as microtubule-poisons. These drugs can be administered in parallel to CNTs, or can be loaded using these as carriers, forming stable covalent bonds or supramolecular assemblies based on noncovalent interactions [ 6 ].…”

“…These drugs can be administered in parallel to CNTs, or can be loaded using these as carriers, forming stable covalent bonds or supramolecular assemblies based on noncovalent interactions [ 6 ]. In most cases, CNTs have the carried drugs physisorbed to their nanotube surfaces by π- π stacking [ 11 , 71 ].…”

Tailoring nano-copolymer/CNTs composite and its application in drug delivery

“…Entezar-Almahdi et al reported that the MWCNTs functionalization is obligatory to improve their preoccupation and bioavailability [15]. Also, González-Lavado et al demonstrated that the use of MWCNTs as a drug delivery system improves the efficiency of used chemotherapy drugs [16].…”

In vitro targeting and selective killing of mcf-7 and colo320dm cells by 5-fluorouracil anchored to carboxylated SWCNTs and MWCNTs

“…Localized tumors can be easily recovered with surgery; however, most of the aggressive cancers are metastasized and develop resistance to chemotherapy [ 3 ]. Therefore, the line of treatment is to use the fixed-dose combinations to inhibit the growth of cells and also to enhance the potential of their cytotoxic effect.…”

“…Moreover, the cost of the anticancer agent(s) is very much high and ultimately, an increase of drug number, will lead to an increase in the cost of the formulation. Paclitaxel and 5-FU can be quoted as a classic example of fixed drug combination used in chemotherapy imparting good anticancer activity but unfortunately, they are interfering with each other [ 3 , 5 ]. In addition, anticancer drugs pose a major issue with the solubility; often in aqueous medium owing to their hydrophobic nature [ 6 ].…”