Abstract
Autophagy plays a key role in human health and disease, especially in cancer and neurodegeneration. Many autophagy regulators are developed for therapy. Diverse nanomaterials have been reported to induce autophagy. However, the underlying mechanisms and universal rules remain unclear. Here, for the first time, we show a reliable and general mechanism by which nanoparticles induce autophagy and then successfully modulate autophagy via tuning their dispersity. Various well-designed univariate experiments demonstrate that nanomaterials induce autophagy in a dispersity-dependent manner. Aggregated nanoparticles induce significant autophagic effect in comparison with well-dispersed nanoparticles. As the highly stable nanoparticles may block autophagic degradation in autolysosomes, endocytosis and intracellular accumulation of nanoparticles can be responsible for this interesting phenomenon. Our results suggest dispersity-dependent autophagic effect as a common cellular response to nanoparticles, reveal the relationship between properties of nanoparticles and autophagy, and offer a new alternative way to modulate autophagy.
Highlights
Plenty of nanoparticles aggregated and precipitated on the surface of cells, which could be visualized by scanning electron microscopy (SEM) (Fig. 1a and Supplementary Figs S1, S2)
Whether mixed IO@DA or IO@dihydroxyphenylacetic acid (DOPAC) nanoparticles with complete medium by pipetting or not, little precipitation was observed on the surface of cells (Supplementary Fig. S13), and LC3-II level was closed to negative control (Fig. 3d)
We have demonstrated that nanoparticles induce autophagy in a dispersity-dependent manner and we could modulate autophagy through tuning the dispersity of nanoparticles
Summary
Up-regulation of these autophagy-related proteins revealed that aggregated nanoparticles caused accumulation of autophagic vacuoles. Investigation by western blot and immunofluorescence revealed that aggregation of nanoparticles induced accumulation of autophagic vacuoles by time and dose dependence (Supplementary Figs S6, S7). Mixing quickly by pipetting or diluting nanoparticles will accelerate diffusion and augment protein adsorption, resulting in diminished aggregation.
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