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Because of its outstanding thermochromic characteristics and metal-insulator transition (MIT) property, nano-vanadium dioxide (abbreviated as nano-VO 2 or nVO 2 ) has been applied widely in electrical/optical devices and design of intelligent window. However, the biological effect of nVO 2 is not well understood, especially when affected by environmental factors or living organisms. For VO 2 is an amphoteric oxide, we simulated pH's influence to nVO 2 's physicochemical properties by exposure nVO 2 in water of different pH values. We found that nVO 2 ransformed to a new product after exposure in acidic water for two weeks, as revealed by physicochemical characterization such as SEM, TEM, XRD, and DLS. This transformation product formed in acidic water was referred as (acidic) transformed nVO 2 ). Both pristine/untransformed and transformed nVO 2 displayed no obvious toxicity to common epithelial cells; however, the acidic transformed nVO 2 rapidly induced macrophage cell death. Further investigation demonstrated that transformed nVO 2 caused macrophage apoptosis by the induction of Ca 2+ efflux and the following mitochondrial membrane permeabilization (MMP) process. And a more detailed time course study indicated that transformed nVO 2 caused lysosomal membrane permeabilization (LMP) at the earlier stage, indicating LMP could be chosen as an earlier and sensitive end point for nanotoxicological study. We conclude that although nVO 2 displays no acute toxicity, its acidic transformation product induces macrophage apoptosis by the induction of LMP and Ca 2+ efflux. This report suggests that the interplay with environmental factors or living organisms can results in physicochemical transformation of nanomaterials and the ensuing distinctive biological effects.

The acidic transformed nano-VO 2 causes macrophage cell death by the induction of lysosomal membrane permeabilization and Ca 2+ efflux