Carbon nanotubes gathered onto silica particles lose their biomimetic properties with the cytoskeleton becoming biocompatible

Elena González-Domínguez,1,* Nerea Iturrioz-Rodríguez,2,* Esperanza Padín-González,2 Juan Villegas,2 Lorena García-Hevia,2 Moisés Pérez-Lorenzo,1 Wolfgang J Parak,3 Miguel A Correa-Duarte,1,* Mónica L Fanarraga2,* 1Department of Physical Chemistry, Biomedical Research Center (CINBIO), Southern Galicia Institute of Health Research (IISSG), Biomedical Research Networking Center for Mental Health (CIBERSAM), Universidade de Vigo, Vigo, Spain; 2Nanomedicine Group, Universidad de Cantabria-IDIVAL, Santander, Spain; 3Department of Physics, Philipps Universität Marburg, Marburg, Germany *These authors contributed equally to this work Abstract: Carbon nanotubes (CNTs) are likely to transform the therapeutic and diagnostic fields in biomedicine during the coming years. However, the fragmented vision of their side effects and toxicity in humans has proscribed their use as nanomedicines. Most studies agree that biocompatibility depends on the state of aggregation/dispersion of CNTs under physiological conditions, but conclusions are confusing so far. This study designs an experimental setup to investigate the cytotoxic effect of individualized multiwalled CNTs compared to that of identical nanotubes assembled on submicrometric structures. Our results demonstrate how CNT cytotoxicity is directly dependent on the nanotube dispersion at a given dosage. When CNTs are gathered onto silica templates, they do not interfere with cell proliferation or survival becoming highly compatible. These results support the hypothesis that CNT cytotoxicity is due to the biomimetics of these nanomaterials with the intracellular nanofilaments. These findings provide major clues for the development of innocuous CNT-containing nanodevices and nanomedicines. Keywords: MWCNTs, biomimetics, cytoskeleton, microtubules, apoptosis, migration, proliferation