Bio-compatibilised carbon nanotubes display significant anti-tumoral effects in solid melanomas

Multiwalled Carbon Nanotubes (MWCNTs) penetrate inside cells binding microtubules and interfering with the cellular biomechanics (1,2). This interaction leads to the formation of biosynthetic tubulin polymers (3,4) that... [ view full abstract ]

Multiwalled Carbon Nanotubes (MWCNTs) penetrate inside cells binding microtubules and interfering with the cellular biomechanics (1,2). This interaction leads to the formation of biosynthetic tubulin polymers (3,4) that display an enhanced stability, and this triggers anti-proliferative (4,5), anti-migratory (6) and cytotoxic (7) effects in different types of cancer cells, leading to antineoplastic effects in solid melanoma tumors (8) in murine models. Moreover, this intrinsic CNT antitumor activity is complementary -and synergetic- to that of traditional microtubule-stabilizing anticancer drugs such as taxol® (paclitaxel)(8). On the other hand, as is also the case for traditional cytotoxic chemotherapy, CNTs can also interfere with the function of heathy cells and produce many unwanted side-effects (9). Consequently, unless most concerns about the toxicity of these materials disappear, the development new treatments based on CNTs offer a poor risk-to-benefit ratio in oncology. Here we demonstrate how mild MWCNTs oxidative treatments enhance intracellular degradation by macrophages while still maintaining the ability of these nanomaterials to interfere with cellular cytoskeletal elements triggering anti-proliferative and cytotoxic processes in cultured cancer cells. Furthermore, we show how single intratumoral dosages of o-MWCNTs produce significant anti-tumoral effects in vivo, in solid malignant melanomas produced by allograft transplantation in murine recipients. We believe these findings have critical implications for the development of new CNT-based nanotherapies to overcome drug resistance in cancer among other applications.

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