Acid-Enhanced Dual-Modal Therapeutic Role Of Metal-Organic Framework-Derived Nanozyme For Efficient Antibacterial Treatment

Bacterial infection has been becoming an increasingly serious global health threat,of which the most widespread treatment is still the application of antibiotics.The abuse of antibiotics will induce the emerge of drug-resistance bacteria and leads to limited therapeutic outcomes.Even worse,the drug-resistance bacteria,just like the "untimed bombs",is possible to break "the last defense" of human beings at any time.The marvelous evolution of nanomaterials in biomedical field provides new path to the antibacterial treatment.Strategies based on reactive oxygen species,photothermal and photodynamic,and metal ions have been developed to achieve effective bacterial killing.However,such single-modal strategies always have limited therapeutic effects or require a high-dose usage.Comparably,dual/multi-modal strategies combining two or more antibacterial method can achieve highly efficient bacterial eradication and reduce the possibility to cause drugresistance.Therefore,research on integrated bacterial eradication with various antibacterial strategies will promote the application of nanomaterials in antibacterial field greatly.Antibacterial strategy based on ROS is known for its rapid and effective sterilization,which is now widely used in the bacterial eradication.But several factors,such as the relatively high pH(-6)in the bacterial infection area,limit the generation of ROS greatly.Researchers have introduced glucose to generate gluconic acid and create an acidic environment in situ,increasing the production of ROS.Nonetheless,it still requires a highdose usage to achieve the ideal bacterial eradication.Metal-organic frameworks(MOFs)are widely used as a carrier in biomedical field to integrate various drugs together.Notably,the metal ions of MOF,such as Ag+,Zn2+,and Cu2+,usually have bacterial killing effect,which makes it an ideal candidate carrier for synergic antibacterial strategies.In this case,we design and fabricate a MOF-based nanozyme to develop an acidenhanced dual-modal antibacterial strategy for highly efficient bacterial eradication.Zeolitic imidazolate frameworks-8(ZIF8),with Zn2+as the ion center,is chosen as the carrier to integrate glucose oxidase(GOx)and gold nanoparticles(Au NPs).The asdesigned nanocatalyst can achieve effective bacterial eradication via the production of ROS and the release of Zn2+.More importantly,gluconic acid,a by-product of the catalytic reaction,can generate an acidic environment(pH≈4).On one hand,the acidic environment can improve the catalytic performance of Au NPs to promote the ROS-producing.On the other hand,the acidic environment can also stimulate the release of Zn2+.So,the generated gluconic acid can enhance the overall bacterial eradication further.At first,the successful synthesis,microstructure and acid-enhanced ROS-producing/Zn2+-releasing ability of ZIF8/Au-GOx NPs have been proved.Systematic antibacterial experiments in vitro have been carried out then to illustrate the superior antibacterial property of ZIF8/Au-GOx.Finally,the wound healing observation proves the effective bacterial eradication in vivo,together with the biocompatibility.