Oncotarget

Research Papers:

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

Eloisa González-Lavado, Lourdes Valdivia, Almudena García-Castaño, Fernando González, Carmen Pesquera, Rafael Valiente, Mónica L. Fanarraga

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Oncotarget. 2019; 10:2022-2029. https://doi.org/10.18632/oncotarget.26770

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Abstract

Eloisa González-Lavado1, Lourdes Valdivia1, Almudena García-Castaño3, Fernando González1, Carmen Pesquera1, Rafael Valiente1,2 and Mónica L. Fanarraga1

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.


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