The increase in autophagic vacuoles in response to nanomaterials may be an adaptive cellular response. There is evidence that autophagy can selectively compartmentalize nanomaterials. In fact, nanoparticles are commonly observed within the autophagosome

compartment, suggesting that activation of autophagy is a targeted exertion to sequester and degrade these materials following entrance into the cytoplasm [104]. It is possible that the cells might perceive nanomaterials as an endosomal pathogen or an aggregation-prone protein (both commonly degraded by the autophagy machinery). Recent evidence Inhibitors,research,lifescience,medical supports ubiquitination of nanomaterials directly Inhibitors,research,lifescience,medical or indirectly via colocalization with ubiquitinated protein aggregates, suggesting that cells may indeed select nanomaterials for autophagy through a pathway similar to invading pathogens [13, 98, 105]. Additionally, ubiquitinated proteins accumulate concomitantly with nanomaterial-induced autophagic vacuoles [106]. It is important to underlie that Inhibitors,research,lifescience,medical nanoscale was a significant factor in eliciting the autophagic response. Autophagy was not induced by quantum dots that had a tendency to aggregate to Caspase activity assay microscale particles into the cells [107]. Nanoscale size dependence was also reported

for neodymium oxide nanoparticle, with larger particles inducing less autophagy [108]. Apparently, modifications of the Inhibitors,research,lifescience,medical surface properties

might be able to alter the autophagy-inducing activity of the nanomaterials. Cationic PAMAM dendrimers elicited autophagy more than anionic ones in vitro [94]. Carbon nanotubes with carboxylic acid group could induce autophagy, while those functionalized with poly-aminobenzene sulfonic acid and polyethylene glycol Inhibitors,research,lifescience,medical groups were not [100]. Recently, it has been published that a short synthetic peptide, RE-1, binds to lanthanide-based nanocrystals, forms a stable coating layer on the nanoparticles surface, and significantly abolishes their autophagy-inducing activity. Furthermore, the addition of an arginine-glycine-aspartic acid motif to RE-1 enhances autophagy induced mafosfamide by lanthanide-based nanocrystals [109]. It is also possible that nanomaterials cause a state of autophagic dysfunction, correlated with a blockade of autophagy flux, and this may be involved in their mechanism of toxicity [110, 111]. Nanoparticles could give rise to autophagy dysfunction by overloading or directly inhibiting lysosomal enzymes or disrupting cytoskeleton-mediated vesicle trafficking, resulting in diminished autophagosome-lysosome fusion [112].