Deciphering active biocompatibility of iron oxide nanoparticles from their intrinsic antagonism

摘要

Magnetite nanoparticles (Fe3O4 NPs) are a well proven biocompatible nanomaterial, which hold great promise in various biomedical applications. Interestingly, unlike conventional biocompatible materials (e.g., polyethylene glycol (PEG)) that are chemically and biologically inert in nature, Fe304 NPs are known to be catalytically active and exhibit prominent physiological effects. Herein, we report an "active", dynamic equilibrium mechanism for maintaining the cellular amenity of Fe304 NPs. We examined the effects of two types of iron oxide (magnetite and hematite) NPs in rat pheochromocytoma (PC12) cells and found that both induced stress responses. However, only Fe203 NPs caused significant programmed cell death; whereas Fe304 NPs are amenable to cells. We found that intrinsic catalase-like activity of Fe3O4 NPs antagonized the accumulation of toxic reactive oxygen species (ROS) induced by themselves, and thereby modulated the extent of cellular oxidative stress, autophagic activity, and programmed cell death. In line with this observation, we effectively reversed severe autophagy and cell death caused by Fe2O3 NPs via co-treatment with natural catalase. This study not only deciphers the distinct intrinsic antagonism of Fe3O4 NPs, but opens new routes to designing biocompatible theranostic nanoparticles with novel mechanisms.