Abstract: Carbon nanotubes are of huge biotechnological interest because they can penetrate most biological barriers and, inside cells, can biomimetically interact with the cytoskeletal filaments, triggering anti-proliferative and cytotoxic effects in highly dividing cells. Unfortunately, their intrinsic properties and bio-persistence represent a putative hazard that relapses their application as therapies against cancer. Here we investigate mild oxidation treatments to improve the intracellular enzymatic digestion of MWCNTs, but preserving their morphology, responsible for their intrinsic cytotoxic properties. Cell imaging techniques and confocal Raman spectroscopic signature analysis revealed that cultured macrophages can degrade bundles of oxidized MWCNTs (o-MWCNTs) in a few days. The isolation of nanotubes from these phagocytes 96 hours after exposure confirmed a significant reduction of approximately 30% in the total length of these filaments compared to the control o-MWCNTs extracted from the cell culture medium, or the intracellular pristine MWCNTs. More interestingly, in vivo single intratumoral injections of o-MWCNTs triggered ca. 30% solid melanoma tumour growth-inhibitory effects while displaying significant signs of biodegradation at the tumoral/peri-tumoral tissues a week after the therapy has had the effect. These results support the potential use of o-MWCNTs as antitumoral agents and reveal interesting clues of how to enhance the efficient clearance of in vivo carbon nanotubes.

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