Distinct autophagy-inducing abilities of similar-sized nanoparticles in cell culture and live C. elegans

Nanomaterial-induced autophagy has raised increasing concerns. A variety of nanomaterials, conventional or recently emerged, have the capability of inducing autophagy. As a consequence, it is becoming a popular belief that induction of autophagy is a common response of cells upon exposure to nanoscale materials. In order to clarify whether the "nanoscale" size is the determining factor for the nanomaterials to induce autophagy, we utilized in vitro cultured cells and an in vivo Caenorhabditis elegans (C. elegans) model to systemically investigate the autophagy-inducing ability of nanomaterials. We selected four types of representative nanomaterials with similar sizes, namely silicon nanoparticles (SiNPs), CdTe quantum dots (QDs), carbon dots (CDs) and gold nanoparticles (AuNPs). We demonstrated that, unlike most other nanomaterials tested, no autophagosome formation was detected in cultured cells or in live C. elegans with SiNP treatment. The expression of autophagy-related genes and the lipidation of LGG-1/LC3 in cells and C. elegans also remained unchanged after the treatment of SiNPs. In addition, the ability of the nanomaterials to induce autophagy appeared to correlate with those to incur subcellular organelle damage. Together, our studies demonstrate that SiNPs do not induce autophagy in vitro or in vivo in the selected model organisms and cell lines, thus clarifying that the "nanoscale" size is not the determining factor for the nanomaterials to induce autophagy. The results also suggest that the autophagy-inducing ability of most nanomaterials could be merely a reflection of their detrimental effect on cellular structures.