Cascade-reaction chemistry can generate reactive-oxygen-species that can be used for the eradication of infectious biofilms.However,suitable and sufficient oxygen sources are not always available near an infection sit...Cascade-reaction chemistry can generate reactive-oxygen-species that can be used for the eradication of infectious biofilms.However,suitable and sufficient oxygen sources are not always available near an infection site,while the reactive-oxygen-species generated are short-lived.Therefore,we developed a magnetic cascade-reaction container composed of mesoporous Fe_(3)O_(4)@SiO_(2) nanoparticles containing glucose-oxidase and L-arginine for generation of reactive-oxygen-species.Glucose-oxidase was conjugated with APTES facilitating coupling to Fe_(3)O_(4)@SiO_(2) nanoparticles and generation of H_(2)O_(2) from glucose.L-arginine was loaded into the nanoparticles to generate NO from the H_(2)O_(2) generated.Using an externally-applied magnetic field,cascade-reaction containers could be homogeneously distributed across the depth of an infectious biofilm.Cascade-reaction containers with coupled glucose-oxidase were effective in killing planktonic,Gram-positive and Gram-negative bacteria.Additional efficacy of the L-arginine based second cascade-reaction was only observed when H_(2)O_(2) as well as NO were generated in-biofilm.In vivo accumulation of cascade-reaction containers inside abdominal Staphylococcus aureus biofilms upon magnetic targeting was observed real-time in living mice through an implanted,intra-vital window.Moreover,vancomycin-resistant,abdominal S.aureus biofilms could be eradicated consuming solely endogenous glucose,without any glucose addition.Herewith,a new,non-antibiotic-based infection-control strategy has been provided,constituting a welcome addendum to the shrinking clinical armamentarium to control antibiotic-resistant bacterial infections.展开更多
基金financially supported by the National Natural Science Foundation of China(51933006,21620102005)The Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2018PT35031).
文摘Cascade-reaction chemistry can generate reactive-oxygen-species that can be used for the eradication of infectious biofilms.However,suitable and sufficient oxygen sources are not always available near an infection site,while the reactive-oxygen-species generated are short-lived.Therefore,we developed a magnetic cascade-reaction container composed of mesoporous Fe_(3)O_(4)@SiO_(2) nanoparticles containing glucose-oxidase and L-arginine for generation of reactive-oxygen-species.Glucose-oxidase was conjugated with APTES facilitating coupling to Fe_(3)O_(4)@SiO_(2) nanoparticles and generation of H_(2)O_(2) from glucose.L-arginine was loaded into the nanoparticles to generate NO from the H_(2)O_(2) generated.Using an externally-applied magnetic field,cascade-reaction containers could be homogeneously distributed across the depth of an infectious biofilm.Cascade-reaction containers with coupled glucose-oxidase were effective in killing planktonic,Gram-positive and Gram-negative bacteria.Additional efficacy of the L-arginine based second cascade-reaction was only observed when H_(2)O_(2) as well as NO were generated in-biofilm.In vivo accumulation of cascade-reaction containers inside abdominal Staphylococcus aureus biofilms upon magnetic targeting was observed real-time in living mice through an implanted,intra-vital window.Moreover,vancomycin-resistant,abdominal S.aureus biofilms could be eradicated consuming solely endogenous glucose,without any glucose addition.Herewith,a new,non-antibiotic-based infection-control strategy has been provided,constituting a welcome addendum to the shrinking clinical armamentarium to control antibiotic-resistant bacterial infections.
