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

// Eloisa González-Lavado 1 , Lourdes Valdivia 1 , Almudena García-Castaño 3 , Fernando González 1 , Carmen Pesquera 1 , Rafael Valiente 1 , 2 and Mónica L. Fanarraga 1 1 Grupo de Nanomedicina, IDIVAL-Universidad de Cantabria, 39011, Santander, Spain 2 Dpto. Física Aplicada, Facultad de Ciencias, Universidad de Cantabria, 39011, Santander, Spain 3 Unidad De Ensayos Clínicos, Oncología Médica y Medicina Paliativa, Hospital Valdecilla-IDIVAL 39011, Santander, Spain Correspondence to: Mónica L. Fanarraga, email: fanarrag@unican.es Keywords: nanomaterial; nanocarrier; drug delivery; combined therapy; microtubule dynamics Received: January 31, 2019 Accepted: February 19, 2019 Published: March 12, 2019 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.