Ferroferric oxide nanoparticles induce prosurvival autophagy in human blood cells by modulating the Beclin 1/Bcl-2/VPS34 complex

Magnetic iron oxide nanoparticles (NPs) are emerging as novel materials with great potentials for various biomedical applications, but their biological activities are largely unknown. In the present study, we found that ferroferric oxide nanoparticles (Fe(3)O(4) NPs) induced autophagy in blood cells. Both naked and modified Fe(3)O(4) NPs induced LC3 lipidation and degraded p62, a monitor of autophagy flux. And this change could be abolished by autophagy inhibitors. Mechanistically, Fe(3)O(4) NP-induced autophagy was accompanied by increased Beclin 1 and VPS34 and decreased Bcl-2, thus promoting the formation of the critical complex in autophagy initiation. Further studies demonstrated that Fe(3)O(4) NPs attenuated cell death induced by anticancer drugs bortezomib and doxorubicin. Therefore, this study suggested that Fe(3)O(4) NPs can induce prosurvival autophagy in blood cells by modulating the Beclin l/Bcl-2/VPS34 complex. This study suggests that caution should be taken when Fe(3)O(4) NPs are used in blood cancer patients.