In-biofilm generation of nitric oxide using a magnetically-targetable cascade-reaction container for eradication of infectious biofilms
By:
Yang, G (Yang, Guang) [1] , [2] , [3] ;
Wang, DY (Wang, Da-Yuan) [1] , [2] , [3] ;
Liu, Y (Liu, Yong) [1] ;
Huang, F (Huang, Fan) [6] , [7] ;
Tian, S (Tian, Shuang) [1] , [2] , [3] ;
Ren, YJ (Ren, Yijin) [4] , [5] ;
Liu, JF (Liu, Jianfeng) [6] , [7] ;
An, YL (An, Yingli) [1] ;
van der Mei, HC (van der Mei, Henny C.) [2] , [3] ;
Busscher, HJ (Busscher, Henk J.) [1] , [2] , [3] ;
Shi, LQ (Shi, Linqi) [1]
DOI
10.1016/j.bioactmat.2022.01.04
Abstract
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 Fe3O4@SiO2 nanoparticles containing glucose-oxidase and t-arginine for generation of reactive-oxygen-species. Glucose-oxidase was conjugated with APTES facilitating coupling to Fe3O4@SiO2 nanoparticles and generation of H2O2 from glucose. L-arginine was loaded into the nanoparticles to generate NO from the H2O2 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 H2O2 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.