Tuning Cell Autophagy by Diversifying Carbon Nanotube Surface Chemistry

Abstract

The induction of autophagy by nanoparticles causes nanotoxicity, but appropriate modulation of autophagy by nanoparticles may have therapeutic potential. Multiwalled carbon nanotubes (MWCNTs) interact with cell membranes and membrane-associated molecules before and after internalization. These interactions alter cellular signaling and impact major cell functions such as cell cycle, apoptosis, and autophagy. In this work, we demonstrated that MWCNT-cell interactions can be modulated by varying densely distributed surface ligands on MWCNTs. Using a fluorescent autophagy-reporting cell line, we evaluated the autophagy induction capability of 81 surface-modified MWCNTs. We identified strong and moderate autophagy-inducing MWCNTs as well as those that did not induce autophagy. Variation of the surface ligand structure of strong autophagy nanoinducers led to the induction of different autophagy-activating signaling pathways, presumably through their different interactions with cell surface receptors.

Mitophagy induced by nanoparticle–peptide conjugates enabling an alternative intracellular trafficking route

“…An elevated autophagy in cells results from stress conditions, which can be induced by a variety of physical, chemical, and biological factors [26e28]. Recently many types of nanomaterials have been reported to introduce autophagic responses in cells [27,29], including quantum dots [30], carbon nanomaterials [31,32], gold or metal oxide nanoparticles [33,34], and polymer nanoparticles [35]. However, mitophagy induced by nanomaterials has not been addressed, nor the demonstration of how this autophagic degradation affects the intracellular trafficking of nanoparticles.…”

Differential autophagic responses to nano-sized materials

“…A battery of 81 multiwalled carbon nanotubes presenting high surface ligand structural diversity was screened to select ligands that enhance LC3 processing [49 ,50]. Interestingly, autophagy induction was observed in cells treated with carbon nanotubes functionalized with surface ligands, but not in cells treated only with the ligands, suggesting that autophagy is activated in response to uptake of the nanomaterials and that the specific nature of the autophagic response depends on the mode of interaction between the nanomaterial and the lysosome-autophagy system [49 ].…”

Titania‐Coated Gold Nano‐Bipyramids for Blocking Autophagy Flux and Sensitizing Cancer Cells to Proteasome Inhibitor‐Induced Death

“…The surface coatings and sizes of nanomaterials are believed to influence their effects on autophagy 12, 13, 17. Among various nanomaterials, gold nanostructures have the advantage of easy control of the surface coatings and particle sizes 20, 21.…”