A triple-enhanced chemodynamic approach based on glucose-powered hybrid nanoreactors for effective bacteria killing

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 H₂O₂ 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 Fe³⁺ and tannic acid (TA). The well-designed nanoreactors could simultaneously break the pH and H₂O₂ 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.