Rapid evolution of multidrug resistance in bacterial pathogens is outpacing the development of new antibiotics,and chemodynamic therapy(CDT)provides an excellent alternative.However,achieving highly efficient CDT is s...Rapid evolution of multidrug resistance in bacterial pathogens is outpacing the development of new antibiotics,and chemodynamic therapy(CDT)provides an excellent alternative.However,achieving highly efficient CDT is still a great challenge,since the pH in the infection site is close to neutral and the supply of H_(2)O_(2)is inadequate.We herein constructed the antibacterial nanoreactors.Indocyanine green(ICG)and glucose oxidase(GOx)were incorporated into homologous zeolitic imidazolate framework-8(ZIF-8)nanoparticles coating with metal polyphenol network(MPN)composed by Fe^(3+)and tannic acid(TA).The well-designed nanoreactors could simultaneously break the pH and H_(2)O_(2)limitations,and generate hyperthermia under irradiation,thus realizing a triple-enhanced CDT for high-efficiency sterilization.Furthermore,the nanoreactors could combine CDT with photothermal therapy(PTT)and photodynamic therapy(PDT),which not only improved the bactericidal efficiency and broadened the antibacterial spectrum,but also alleviated the antibiotics resistance issues.Remarkably,the proposed nanoreactors achieved a robust in vitro bacterial killing against Gram-positive methicillin-resistant Staphylococcus aureus(MRSA)and Gram-negative Pseudomonas aeruginosa.The nanoreactors achieved an 99.7%MRSA reduction in an MRSA-induced murine abscess model accompanied with negligible toxicity.Overall,this study provides a promising strategy for multiple-enhanced CDT and multimodal combined therapy for pathogenic infections.展开更多
基金supported by the National Natural Science Foundation of China(No.82173747)the Guangdong Basic and Applied Basic Research Foundation(No.2022B1515020085)+1 种基金the Natural Science Foundation of Guangdong Province(No.2021A1515012525)the Science and Technology Plan Projects of Guangzhou(No.202102020635).
文摘Rapid evolution of multidrug resistance in bacterial pathogens is outpacing the development of new antibiotics,and chemodynamic therapy(CDT)provides an excellent alternative.However,achieving highly efficient CDT is still a great challenge,since the pH in the infection site is close to neutral and the supply of H_(2)O_(2)is inadequate.We herein constructed the antibacterial nanoreactors.Indocyanine green(ICG)and glucose oxidase(GOx)were incorporated into homologous zeolitic imidazolate framework-8(ZIF-8)nanoparticles coating with metal polyphenol network(MPN)composed by Fe^(3+)and tannic acid(TA).The well-designed nanoreactors could simultaneously break the pH and H_(2)O_(2)limitations,and generate hyperthermia under irradiation,thus realizing a triple-enhanced CDT for high-efficiency sterilization.Furthermore,the nanoreactors could combine CDT with photothermal therapy(PTT)and photodynamic therapy(PDT),which not only improved the bactericidal efficiency and broadened the antibacterial spectrum,but also alleviated the antibiotics resistance issues.Remarkably,the proposed nanoreactors achieved a robust in vitro bacterial killing against Gram-positive methicillin-resistant Staphylococcus aureus(MRSA)and Gram-negative Pseudomonas aeruginosa.The nanoreactors achieved an 99.7%MRSA reduction in an MRSA-induced murine abscess model accompanied with negligible toxicity.Overall,this study provides a promising strategy for multiple-enhanced CDT and multimodal combined therapy for pathogenic infections.
