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

Abstract

Min Shi,1,* Liang Cheng,2,* Zubin Zhang,1 Zhuang Liu,2 Xinliang Mao1,31Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Department of Pharmacology, College of Pharmaceutical Sciences, 2Functional Nano and Soft Material (FUNSOM), Collaborative Innovation Center of Suzhou, Nano Science and Technology, 3Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, People’s Republic of China*These authors contributed equally to this studyAbstract: 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 (Fe3O4 NPs) induced autophagy in blood cells. Both naked and modified Fe3O4 NPs induced LC3 lipidation and degraded p62, a monitor of autophagy flux. And this change could be abolished by autophagy inhibitors. Mechanistically, Fe3O4 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 Fe3O4 NPs attenuated cell death induced by anticancer drugs bortezomib and doxorubicin. Therefore, this study suggested that Fe3O4 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 Fe3O4 NPs are used in blood cancer patients.Keywords: iron oxide nanoparticle, autophagic pathway, anti-apoptosis