Hydrogen Sulfide Responsive Metal-organic Framework Materials For Enhanced Antibacterial Properties Of Antibiotics

Objective:Metal-organic framework UiO-66-NH2 has low biotoxicity,good structural stability,and is an excellent drug delivery vehicle.However,the endogenous hydrogen sulfide produced by bacteria can protect them from antibiotic-induced damage.In this study,we propose to modify UiO-66-NH2 with maleic anhydride to prepare new antibiotic-loaded nanomaterials,inactivate the endogenous hydrogen sulfide produced by bacteria,enhance the susceptibility of bacteria to the action of antibiotics,achieve antibacterial effects,and provide new research solutions as well as ideas for the design of new antibacterial materials.Methods:(1)Firstly,the yellowish UiO-66-MA was prepared by reflux reaction using UiO-66-NH2 and maleic anhydride;(2)UiO-66-MA was dispersed in methanolic solution of gentamicin by sonication to obtain UiO-66-MA@Gm;(3)A series of instrumentation was used to characterize UiO-66-NH2,UiO-66-MA,UiO-66-MA@Gm;(4)Assessing the biosafety of the antimicrobial materials by MTT and hemolysis assays;(5)Testing the antibiotic release efficiency and process of the antimicrobial nanomaterials;(6)Testing the amount of H2S produced by bacteria and the amount of H2S remaining after the Michael addition reaction between the H2S produced by bacteria and their Michael addition reaction with increasing concentrations of UiO-66-MA by lead acetate test paper;(7)Combining UiO-66-MA@Gm and UiO-66-MA@Gm after treatment with sodium sulfide were incubated with Escherichia coli and Pseudomonas aeruginosa,and the antibacterial activity of UiO-66-MA@Gm was studied by dilution smear plate counting to investigate the susceptibility of antibacterial nanomaterials to the antibacterial effect of antibiotics;(8)UiO-66-MA@Gm was incubated with incubated Pseudomonas aeruginosa biofilms.The biofilm inhibitory effect of UiO-66-MA@Gm was studied by dilution smear plate counting;(9)An animal model of E.coli infection was constructed,and the antibacterial activity and sensitivity of the nanomaterials to the enhanced antibiotic antibacterial effect were systematically investigated by detecting the bacterial population and wound repair at the infected wound site.Results:(1)UiO-66-MA nanomaterials were successfully prepared by modifying UiO-66-NH2 MOFs with maleic anhydride to obtain UiO-66-MA nanomaterials,and new antibacterial nanomaterials UiO-66-MA@Gm were obtained by loading gentamicin(Gm);(2)Bacteria can spontaneously produce H2S,and the detection of the reaction between UiO-66-MA and bacterial H2S by lead acetate test paper showed that as the UiO-66-MA content increases,the H2S content produced by bacteria decreases.(3)The release efficiency of gentamicin within UiO-66-MA@Gm was as high as 92%,indicating that the antibacterial nanomaterials can release antibiotics stably and efficiently;(4)The nanomaterials were co-incubated with Escherichia coli and Pseudomonas aeruginosa,respectively,and the results showed that the nanomaterials have good antibacterial properties;the content of bacterial endogenous H2S decreased in bacteria treated with UiO-66-MA,thus reduce bacterial resistance to antibiotics and enhance antibiotic sensitivity;(5)The nanomaterials were incubated with Pseudomonas aeruginosa biofilm,and the results showed that UiO-66-MA@Gm antimicrobial nanomaterials had good inhibitory effect on Pseudomonas aeruginosa biofilm;(6)The animal wound model of E.coli infection revealed that the antimicrobial nanomaterials had good antimicrobial therapeutic effect.Conclusion:The new antimicrobial nanomaterial composed of UiO-66-MA loaded with antibiotics can perform Michael addition reaction with endogenous H2S produced by bacteria,thus reducing the content of endogenous H2S produced by bacteria,reducing the self-protection effect of bacteria and resistance to antibiotics,enhancing the sensitivity of antibiotics to bacteria,and achieving good antimicrobial effect.