Silica-coated Zinc Ferrite Nanoparticles For Anti-helicobacter Pylori Therapy In Vitro And Biosecurity In Vivo

Objective:To investigate the antimicrobial effect of silica-coated zinc ferrite nanoparticles as a new therapeutic agent against Helicobacter pylori(H.pylori)in vitro and biosecurity in vivo under an alternating magnetic field(AMF).Methods:1.The physical characterization,composition and magnetic properties of Zinc ferrite nanoparticles(Zn0.5Fe2.5O4)and silica-coated zinc ferrite nanoparticles(Zn0.5Fe2.5O4@SiO2)were tested by transmission electron microscopy and X-ray diffractometer.The heating efficiency was observed in vitro.2.The cytotoxicity of Zn0.5Fe2.5O4@SiO2 was evaluated by CCK-8 assay using a gastric cancer cell line SCC-7901.3.H.pylori strain NCTC11637 was incubated in Karmali growth medium containing Zn0.5Fe2.5O4@SiO2.Upon exposure to an AMF(430kHz,31kA/m)in vitro,H.pylori was heated to variable temperature for variable time.Changes in H.pylori colonization were detected by visible ultraviolet spectrophotometer.Karmali growth medium containing amoxicillin of series of concentration was prepared and minimum inhibitory concentration(MIC)of amoxicillin before and after heating were determined by agar dilution method.4.C57BL/6 mouse model for in vivo temperature measurement was built and the heating efficiency of Zn0.5Fe2.5O4@SiO2 in vivo was assessed.5.Female C57BL/6 mice were randomly divided into heating group,MNPs group and control group.And the heating group comprised four subgroups of different doses of MNPs:10mg/kg,25mg/kg,50mg/kg and 100mg/kg.Zn0.5Fe2.5O4@SiO2 was given by gavage in heating group and MNPs group.The same amount of deionized water was given by gavage in control group.The heating group was then put in an AMF and instant temperature in vivo was monitored via a temperature measurement probe while the control group stayed unprocessed.After heating for ten minutes at 43 ?,three groups were sacrificed and histopathological analysis was carried out to compare the pathological changes between groups.Results:1.The core/shell-structured Zn0.5Fe2,504@SiO2 was uniform in size and satisfactorily superparamagnetic.2.Zn0.5Fe2.5O4@SiO2 showed no cytotoxicity below 500?g/ml after 24h and 48h in contact with SGC-7901 cell lines,only the highest concentration(700?g/ml)causing significant decrease in cell survival rates.3.Compared with non-heating group,H.pylori growth was inhibited for 60%and 80%after 10 minutes and 15minutes of magnetic heating at 43 ?,respectively.We also observed the synergy effect of Zn0.5Fe2.5O4@SiO2 with Amoxicillin against H.pylori strains NCTC11637.The MIC of amoxicillin alone was 0.048?g/ml.Upon exposure to an AMF(430kHz,31kA/m)?however,the figure dropped to 0.023 pg/ml at 43 ? for 10-15 minutes of heating.4.The heating efficiency in vivo was improved with the increasing doses of MNPs.Heating from basal body temperature to 43 ? at doses of 10mg/kg,25mg/kg,50mg/kg and 1 00mg/kg costed>20min,9-11 min,3-6min and<1 min,respectively.5.Under the heating condition of 43 ? for 10 minutes,the stomach of C57BL/6 mice in l0mg/kg and 25mg/kg subgroups showed no pathological injury compared with the control group.However,the inflammatory response was observed in 50mg/kg and 1 00mg/kg subgroups.Conclusion:Zn0.5Fe2.5O4@SiO2 was effective at inhibiting the H.pylori and enhancing the therapeutic effect of amoxicillin by magnetic nanoparticles-induced hyperthermia.Magnetic hyperthermia in vivo can be achieved without inducing pathological damage under appropriate doses and heating condition.