Microtubule cytoskeleton-disrupting activity of MWCNTs: applications in cancer treatment
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ournal of Nanobiotechnology Open Access
REVIEW
Microtubule cytoskeleton‑disrupting activity of MWCNTs: applications in cancer treatment Lorena García Hevia and Mónica L. Fanarraga*
Abstract Microtubules and carbon nanotubes (CNTs), and more particularly multi-walled CNTs (MWCNTs), share many mechanical and morphological similarities that prompt their association into biosynthetic tubulin filaments both, in vitro and in vivo. Unlike CNTs, microtubules are highly dynamic protein polymers that, upon interaction with these nanomaterials, display enhanced stability that has critical consequences at the cellular level. Among others, CNTs prompt ectopic (acentrosomal) microtubule nucleation and the disassembly of the centrosome, causing a dramatic cytoskeletal reorganization. These changes in the microtubule pattern trigger the generation of ineffective biomechanical forces that result in migration defects, and ultimately in spindle-assembly checkpoint (SAC) blockage and apoptosis. In this review, we describe the molecular mechanism involved in the intrinsic interference of CNTs with the microtubule dynamics and illustrate the consequences of this effect on cell biomechanics. We also discuss the potential application of these synthetic microtubule-stabilizing agents as synergetic agents to boost the effect of classical chemotherapy that includes spindle poisons (i.e. paclitaxel) or DNA interfering agents (5-fluorouracil)-, and list some of the advantages of the use of MWCNTs as adjuvant agents in preventing cell resistance to chemotherapy. Carbon nanotubes Carbon nanotubes (CNTs) are materials with exceptional properties from the physicochemical point of view that are becoming increasingly important in the field of nanobiotechnology. Their reactive surface allows these nanofilaments to capture large amounts of biomolecules on their corona [1–3]. This CNT proteinaceous coating behaves as biological camouflage that endows the nanotubes with the ability to selectively interact with receptor proteins or participating in specific protein-protein interactions [2, 4, 5]. CNTs are also well-known to adsorb many different types of inorganic molecules or drugs [6–16] or nucleic acids [9, 17] all of the great interest in nanomedicine. Finally, at the elementary level, CNTs are
*Correspondence: [email protected] Nanomedicine Group, Valdecilla Research Institute-IDIVAL, University of Cantabria, Herrera Oria s/n, 39011 Santander, Spain
pure carbon and this composition makes them highly biocompatible since carbon represents ca. 18% of the composition of the human body. Another interesting feature of CNTs is their onedimensional morphology. This property—very attractive from a biotechnological point of view—endows nanotubes with the unique ability to penetrate inside cells and cross tissues. But, from a biotechnological level, this feature represents a double edge sword since, CNTs can penetrate through most biological barriers causing putative potential long-term effects. This fact, in addition to their bio-persistence, are some
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