Abstract: Despite notable progress in cancer therapy, metastatic diseases continue to be the primary cause of cancer-related mortality. Multi-walled carbon nanotubes (MWCNTs) can enter tissues and cells and interfere with the dynamics of the cytoskeletal nanofilaments biomimetically. This endows them with intrinsic anti-tumoral effects comparable to those of microtubule-binding chemotherapies such as Taxol®. In this study, our focus was on exploring the potential of oxidized MWCNTs in selectively targeting the vascular endothelial growth factor receptor (VEGFR). Our objective was to evaluate their effectiveness in inhibiting metastatic growth by inducing anti-proliferative, anti-migratory, and cytotoxic effects on both cancer and tumor microenvironment cells. Our findings demonstrated a significant reduction of over 80 % in malignant melanoma lung metastases and a substantial enhancement in overall animal welfare following intravenous administration of the targeted biodegradable MWCNTs. Furthermore, the combination of these nanomaterials with the conventional chemotherapy agent Taxol® yielded a remarkable 90 % increase in the antimetastatic effect. These results highlight the promising potential of this combined therapeutic approach against metastatic disease and are of paramount importance as metastasis is responsible for nearly 60,000 deaths each year.

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