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In-biofilm generation of nitric oxide using a magnetically-targetable cascade-reaction container for eradication of infectious biofilms.

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 l-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.

SUBMITTER: Yang G

PROVIDER: S-EPMC8964971 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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In-biofilm generation of nitric oxide using a magnetically-targetable cascade-reaction container for eradication of infectious biofilms.

Yang Guang G Wang Da-Yuan DY Liu Yong Y Huang Fan F Tian Shuang S Ren Yijin Y Liu Jianfeng J An Yingli Y van der Mei Henny C HC Busscher Henk J HJ Shi Linqi L

Bioactive materials 20220210

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 l-arginine for generation of reactive-oxyge ...[more]

PMID: 35386819

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Project description:Magnetically driven robots can perform complex functions in biological settings with minimal destruction. However, robots designed to damage deleterious biostructures could also have important impact. In particular, there is an urgent need for new strategies to eradicate bacterial biofilms as we approach a post-antibiotic era. Biofilms are intractable and firmly attached structures ubiquitously associated with drug-resistant infections and destruction of surfaces. Existing treatments are inadequate to both kill and remove bacteria leading to reinfection. Here we design catalytic antimicrobial robots (CARs) that precisely and controllably kill, degrade and remove biofilms with remarkable efficiency. CARs exploit iron oxide nanoparticles (NPs) with dual catalytic-magnetic functionality that (i) generate bactericidal free radicals, (ii) breakdown the biofilm exopolysaccharide (EPS) matrix, and (iii) remove the fragmented biofilm debris via magnetic field driven robotic assemblies. We develop two distinct CAR platforms. The first platform, the biohybrid CAR, is formed from NPs and biofilm degradation products. After catalytic bacterial killing and EPS disruption, magnetic field gradients assemble NPs and the biodegraded products into a plow-like superstructure. When driven with an external magnetic field, the biohybrid CAR completely removes biomass in a controlled manner, preventing biofilm regrowth. Biohybrid CARs can be swept over broad swathes of surface or can be moved over well-defined paths for localized removal with microscale precision. The second platform, the 3D molded CAR, is a polymeric soft robot with embedded catalytic-magnetic NPs, formed in a customized 3D printed mold to perform specific tasks in enclosed domains. Vane-shaped CARs remove biofilms from curved walls of cylindrical tubes, and helicoid-shaped CARs drill through biofilm clogs, while simultaneously killing bacteria. In addition, we demonstrate applications of CARs to target highly confined anatomical surfaces in the interior of human teeth. These 'kill-degrade-and-remove' CARs systems could have significant impact in fighting persistent biofilm-infections and in mitigating biofouling of medical devices and diverse surfaces.

Dataset Information

In-biofilm generation of nitric oxide using a magnetically-targetable cascade-reaction container for eradication of infectious biofilms.

Publications

In-biofilm generation of nitric oxide using a magnetically-targetable cascade-reaction container for eradication of infectious biofilms.

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