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Cerebral ischemic stroke stimulates excessive reactive oxygen species, which lead to blood-brain-barrier disruption, neuron death, and aggravated cerebral infarction. Thus, it is critical to develop an antioxidant strategy for stroke treatment. Herein, we report a dietary strategy to promote stroke healing using iron oxide (Fe3O4) nanoparticles with intrinsic enzyme-like activities. We find that Fe3O4 nanozymes exhibit triple enzyme-like activities, peroxidase, catalase, and superoxide dismutase, thus potentially possessing the ability to regulate the ROS level. Importantly, intragastric administration of PEG-modified Fe3O4 nanozymes significantly reduces cerebral infarction and neuronal death in a rodent model following cerebral ischemic stroke. Ex vivo analysis shows that PEG-modified Fe3O4 nanozymes localize in the cerebral vasculature, ameliorate local redox state with decreased malondialdehyde and increased Cu/Zn SOD, and facilitate blood-brain-barrier recovery by elevating ZO-1 and Claudin-5 in the hippocampus. Altogether, our results suggest that dietary PEG-modified Fe3O4 nanozymes can facilitate blood-brain-barrier reconstruction and protect neurons following ischemic stroke.

Influenza poses a severe threat to human health in the world. However, developing a universal anti-viral strategy has remained challenging due to the presence of diverse subtypes as well as its high mutation rate, resulting in antigenic shift and drift. Here we developed an antiviral strategy using iron oxide nanozymes (IONzymes) to target the lipid envelope of the influenza virus. Methods: We evaluated the antiviral activities of our IONzymes using a hemagglutination assay, together with a 50% tissue culture infectious doses (TCID50) method. Lipid peroxidation of the viral envelope was analyzed using a maleic dialdehyde (MDA) assay and transmission electron microscopy (TEM). The neighboring viral proteins were detected by western blotting. Results: We show that IONzymes induce envelope lipid peroxidation and destroy the integrity of neighboring proteins, including hemagglutinin, neuraminidase, and matrix protein 1, causing the inactivation of influenza A viruses (IAVs). Furthermore, we show that our IONzymes possess a broad-spectrum antiviral activity on 12 subtypes of IAVs (H1~H12). Lastly, we demonstrate that applying IONzymes to a facemask improves the ability of virus protection against 3 important subtypes that pose a threat to human, including H1N1, H5N1, and H7N9 subtype. Conclusion: Together, our results clearly demonstrate that IONzymes can catalyze lipid peroxidation of the viral lipid envelope to inactivate enveloped viruses and provide protection from viral transmission and infection.

Mouth ulcer is associated with inflammation and high risk of bacterial infection, which aggravates the patient’s condition. Currently, there is no effective treatment for mouth ulcer. Herein, we report that vitamin-modified iron oxide nanoparticles improve the healing of mouth ulcer through anti-inflammation and antibacterial activities. We discovered that vitamin B2 (VB2) modified iron oxide nanoparticles performed enhanced peroxidase-like, catalase-like, and superoxide dismutase (SOD)-like activities, acting as typical iron oxide nanozymes (IONzymes) with triad activities. In particular, VB2 modification significantly improved the SOD-like activity, thus providing a reactive oxygen species (ROS)-scavenging ability. Cellular antioxidant experiments showed that vitamin B2 modified IONzymes (VB2-IONzymes) protect human oral keratinocytes (HOK) and BALB/3T3 cells from hydrogen peroxide (H2O2), and these cells have high biocompatibility to eukaryotic cells. In addition, VB2-IONzymes exerted an antibacterial activity against Streptococcus mutans , Staphylococcus aureus , and Escherichia coli . Importantly, VB2-IONzymes accelerated the recovery of mouth ulcer and reduced the local secretion of inflammatory factors in mouse ulcer model via ROS scavenging and antibacterial activity. Taken together, our work demonstrates that vitamin B2 modification endows iron oxide nanoparticles with enhanced enzyme-like activities and VB2-IONzymes may be a promising reagent in the treatment of mouth ulcer because of their intrinsic anti-inflammation and antibacterial capabilities.

Bacteria can increase drug resistance by forming bacterial biofilms. Once the biofilm is formed, it becomes difficult to remove or kill the related bacteria completely by antibiotics and other antibacterial agents because these antibacterial agents cannot easily break through the biofilm matrix barrier and reach the internal bacteria. Therefore, we synthesized magnetite hybrid nanocomplexes that can penetrate and disrupt bacterial biofilms. The obtained nanocomposites are composed of multinucleated iron oxides and Ag seeds. The outer iron oxides can help the internal Ag nanoparticles penetrate the bacterial biofilms, hence killing the internal bacteria and disrupting the biofilms. We took advantage of E. coli and P. aeruginosa bacteria to test the antibacterial properties of the magnetite hybrid nanocomplexes. When planktonic E. coli and P. aeruginosa bacteria were incubated with 100 μg mL-1 magnetite hybrid nanocomplexes for 30 min, almost all the bacteria were killed. When the obtained biofilms of E. coli and P. aeruginosa were treated with magnetite hybrid nanocomplexes (10 μg mL-1 and 100 μg mL-1), the survival of E. coli and P. aeruginosa biofilms with a magnetic field showed a big decrease compared with that without a magnetic field. Therefore, the as-synthesized nanocomposites have promising potential as antimicrobial agents for killing bacteria and disrupting biofilms in the presence of a magnetic field, and thus should be further studied for a wide range of antibacterial applications.

The use of natural substance to ward off microbial infections has a long history. However, the large-scale production of natural extracts often reduces antibacterial potency, thus limiting practical applications. Here we present a strategy for converting natural organosulfur compounds into nano-iron sulfides that exhibit enhanced antibacterial activity. We show that compared to garlic-derived organosulfur compounds nano-iron sulfides exhibit an over 500-fold increase in antibacterial efficacy to kill several pathogenic and drug-resistant bacteria. Furthermore, our analysis reveals that hydrogen polysulfanes released from nano-iron sulfides possess potent bactericidal activity and the release of polysulfanes can be accelerated by the enzyme-like activity of nano-iron sulfides. Finally, we demonstrate that topical applications of nano-iron sulfides can effectively disrupt pathogenic biofilms on human teeth and accelerate infected-wound healing. Together, our approach to convert organosulfur compounds into inorganic polysulfides potentially provides an antibacterial alternative to combat bacterial infections.