Palladium nanoparticles induce autophagy and autophagic flux blockade in Hela cells

Abstract

Autophagy is a lysosome-based degradative pathway associated with cancer. As a novel class of autophagy activator, nanoparticles (NPs) have been recently found to have potential applications in clinical therapy. Palladium nanoparticles (PdNPs), which have unique physical and chemical properties, have been used in biosensing and biological imaging. In the present study, size-dependent PdNPs-induced autophagy and autophagic flux blockade in Hela cells were investigated. By monitoring the transformation of autophagosome marker protein LC3, the intensity of fluorescence labeling and the quantity of autophagosomes, autophagosome accumulation with increasing concentration and varying size of PdNPs was observed. The slowed degradation of autophagy substrate p62 and long-lived proteins together with the impairment of lysosomes indicates that PdNPs treatment results in a decrease of the degradation capability of lysosomes and blockade of autophagic flux. In this work, PdNPs were found to affect autophagosome accumulation in two ways. One is led by autophagy activated through the mTOR signaling pathway at low concentration, and another is dominated by autophagic flux blockade resulting from lysosome impairment at high concentration. Autophagy in Hela cells could be effectively regulated by controlling the concentration and size of PdNPs; this provides an important reference for future applications of PdNPs in biomedicine.