Biodegradable multi-walled carbon nanotubes trigger anti-tumoral effects

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.

Multi-walled carbon nanotubes complement the anti-tumoral effect of 5-Fluorouracil

“…Their similarities prompt interaction in vitro [8] and in vivo [9], and the assemblage mixed functional bio-synthetic tubulin polymers that display an enhanced stability compared to conventional microtubules [10]. The increased stability of these mixed polymers causes critical changes in the cellular biomechanics, triggering the reported anti-proliferative [9, 11], anti-migratory [12–14] and cytotoxic effects in vitro in cancer cells [15–17], and significant anti-tumoral effects in vivo [18, 19]. In addition, some studies show how MWCNTs are effective in cells and tumors that have developed resistance to Taxol ® [18].…”

Hydrolytic degradation and cytotoxicity of poly(lactic‐co‐glycolic acid)/multiwalled carbon nanotubes for bone regeneration

“…One of the inconveniences of carbon nanotubes is that they are not biodegradables; however, it has been experimentally demonstrated in vivo that they can be excreted and therefore disappear from the human body when no longer necessary . Recent studies have centered on biocompatibility of these materials, improving their biodegradability, although maintaining their anti‐tumoral effects given that in vitro tests demonstrated an anti‐proliferative, anti‐migratory, and cytotoxic capability .…”

“…One of the inconveniences of carbon nanotubes is that they are not biodegradables; however, it has been experimentally demonstrated in vivo that they can be excreted and therefore disappear from the human body when no longer necessary . Recent studies have centered on biocompatibility of these materials, improving their biodegradability, although maintaining their anti‐tumoral effects given that in vitro tests demonstrated an anti‐proliferative, anti‐migratory, and cytotoxic capability . Another of their inconveniences is their cytotoxicity, as they can contain remains of catalyzers and carbon deposits on the outside of the nanotube, due to their synthesis, although any such traces will disappear when they are purified and functionalized with various methods, such as refluxing in nitric acid …”

Engineering Sub-Cellular Targeting Strategies to Enhance Safe Cytosolic Silica Particle Dissolution in Cells

“…The coating with oxidized CNTs is indicated in Section 2.2. Particle dosages and exposure times have been fully characterized in previous studies [25,28].…”

“…Oxidized CNT coating was performed on poly-l-lysine coated MSP. A full characterization of the batch of nanotubes (from Nanocyl, ref: NC3100™) is available in the previous publications of the group [25,26,28]. In short, MSP were electrostatically attached to the particles.…”