Dual Enzyme-like Activities of Iron Oxide Nanoparticles and Their Implication for Diminishing Cytotoxicity

Iron oxide nanoparticles (IONPs) are frequently used in biomedical applications, yet their toxic potential is still a major concern. While most studies of biosafety focus on cellular responses after exposure to nanomaterials, little is reported to analyze reactions on the surface of nanoparticles as a source of cytotoxicity. Here we report that different intracellular microenvironment in which IONPs are located leads to contradictive outcomes in their abilities to produce free radicals. We first verified pH-dependent peroxidase-like and catalase-like activities of IONPs and investigated how they interact with hydrogen peroxide (H₂O₂) within cells. Results showed that IONPs had a concentration-dependent cytotoxicity on human glioma U251 cells, and they could enhance H₂O₂-induced cell damage dramatically. By conducting electron spin resonance spectroscopy experiments, we showed that both Fe₃O₄ and γ-Fe₂O₃ nanoparticles could catalyze H₂O₂ to produce hydroxyl radicals in acidic lysosome mimic conditions, with relative potency Fe₃O₄ > γ-Fe₂O₃, which was consistent with their peroxidase-like activities. However, no hydroxyl radicals were observed in neutral cytosol mimic conditions with both nanoparticles. Instead, they decomposed H₂O₂ into H₂O and O₂ directly in this condition through catalase-like activities. Transmission electron micrographs revealed that IONPs located in lysosomes in cells, the acidic environment of which may contribute to hydroxyl radical production. This is the first study regarding cytotoxicity based on their enzyme-like activities. Since H₂O₂ is continuously produced in cells, our data indicate that lysosome-escaped strategy for IONP delivery would be an efficient way to diminish long-term toxic potential

Prussian Blue Nanoparticles as Multienzyme Mimetics and Reactive Oxygen Species Scavengers

The generation of reactive oxygen species (ROS) is an important mechanism of nanomaterial toxicity. We found that Prussian blue nanoparticles (PBNPs) can effectively scavenge ROS via multienzyme-like activity including peroxidase (POD), catalase (CAT), and superoxide dismutase (SOD) activity. Instead of producing hydroxyl radicals (•OH) through the Fenton reaction, PBNPs were shown to be POD mimetics that can inhibit •OH generation. We theorized for the first time that the multienzyme-like activities of PBNPs were likely caused by the abundant redox potentials of their different forms, making them efficient electron transporters. To study the ROS scavenging ability of PBNPs, a series of in vitro ROS-generating models was established using chemicals, UV irradiation, oxidized low-density lipoprotein, high glucose contents, and oxygen glucose deprivation and reperfusion. To demonstrate the ROS scavenging ability of PBNPs, an in vivo inflammation model was established using lipoproteins in Institute for Cancer Research (ICR) mice. The results indicated that PBNPs hold great potential for inhibiting or relieving injury induced by ROS in these pathological processes

Sources and Processes Affecting Fine Particulate Matter Pollution over North China: An Adjoint Analysis of the Beijing APEC Period

The stringent emission controls during the APEC 2014 (the Asia-Pacific Economic Cooperation Summit; November 5–11, 2014) offer a unique opportunity to quantify factors affecting fine particulate matter (PM_2.5) pollution over North China. Here we apply a four-dimensional variational data assimilation system using the adjoint model of GEOS-Chem to address this issue. Hourly surface measurements of PM_2.5 and SO₂ for October 15-November 14, 2014 are assimilated into the model to optimize daily aerosol primary and precursor emissions over North China. Measured PM_2.5 concentrations in Beijing average 50.3 μg m^–3 during APEC, 43% lower than the mean concentration (88.2 μg m^–3) for the whole period including APEC. Model results attribute about half of the reduction to meteorology due to active cold surge occurrences during APEC. Assimilation of surface measurements largely reduces the model biases and estimates 6%–30% lower aerosol emissions in the Beijing–Tianjin–Hebei region during APEC than in late October. We further demonstrate that high PM_2.5 events in Beijing during this period can be occasionally contributed by natural mineral dust, but more events show large sensitivities to inorganic aerosol sources, particularly emissions of ammonia (NH₃) and nitrogen oxides (NO_<i>x</i>) reflecting strong formation of aerosol nitrate in the fall season