Antioxidant Function Of Prussian Blue Nanoparticles Based On Their Multienzyme-like Activities

In recent years,a lot of metal based nanomaterials have been found to possess natural enzyme-like activities and can be used as enzyme mimetics in biomedical fields including in vitro detection,in vivo imaging,tumor therapy and so on.In this paper,we systemically studied the enzyme-like activities of Prussian blue nanoparticles(PBNPs)and the corresponding mechanisms;furthermore,we applied PBNPs in antioxidation and explored the biosafety of PBNPs.The main results of this dissertation are summaried as following:(1)We synthesized PBNPs and studied their enzyme-like activities including peroxidase(POD),catalase(CAT),superoxide dismutase(SOD)and ascorbic acid oxidase(AAO).Then we found the POD-like acitivity of PBNPs is much higher than iron oxide nanoparticles,moreover,unlike IONPs,POD-like acitivity of PBNPs does not follow Fenton reaction mechanism,instead,we theorized for the first time that the POD-like activity of PBNPs were likely caused by the abundant redox potentials of their different forms,which make PBNPs efficient electron transporters.Further study showed that the CAT-,SOD-and AAO-like activities of PBNPs also follow the electron transporting mechanism.(2)In order to study the ROS scavenging ability of PBNPs,we established a series of in vitro ROS-generating models by using diallyl trisulfide(DATS),cisplatin(CDDP),UV irradiation,oxidized low-density lipoprotein(OxLDL),high glucose contents(HG),and oxygen glucose deprivation and reperfusion(HT),phorbol 12 myristate 13 acetate(PMA),lipopolysaccharide(LPS).Moreover,an in vivo inflammation model was established using LPS in Institute for Cancer Research(ICR)mice and a diabetes mellitus model was established using streptozotocin(STZ)in C57 BL/6J mice.The results indicated that PBNPs hold great potential for inhibiting injury induced by excessive ROS in these pathological processes.(3)We systematically studied the biosafety of PBNPs in vivo.We studied the in vivo behaviors of PBNPs by tissue iron content measurement,tissue staining and magnetic resonance imaging(MRI).From the biological distribution data we found that PBNPs mainly accumulated in the mononuclear phagocytic system(MPS)including liver and spleen after intravenous administration.By measuring the iron content in urine and feces,we concluded the PBNPs could be gradually cleared out by both renal and fecal excretion.PBNPs did not cause appreciable toxicity to the treated ICR mice at our tested dose(150 mg/kg/d,intraperitoneal injection for 30 days)according to hematology analysis,blood biochemical analysis and histological examinations.However,the half lethal dose(LD50)of PBNPs via tail vein injection is 41.92mg/kg,the acute toxicity maybe caused by the accumulation of PBNPs in lung,which damaged the respiratory function.Reducing the size of PBNPs could lower the accumulation quantity and toxicity.Overall,the data for the biosafety evaluation is encouraging.There are few reports on the research for catalytic mechanism of nanozymes in the domestic and overseas,while our study provides a new direction for the related research.Furthermore,our results greatly promote the biomedical applications of PBNPs.