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.

细菌病原体中多药耐药性的快速发展超过了新抗生素的开发速度，化学动力学疗法 (CDT) 提供了一种极好的替代方案。然而，实现高效的 CDT 仍然是一个巨大的挑战，因为感染部位的 pH 值接近中性并且 H ₂ O ₂的供应不足。我们在此构建了抗菌纳米反应器。吲哚菁绿（ICG）和葡萄糖氧化酶（GOx）被掺入到由Fe ³⁺和单宁酸（TA）组成的金属多酚网络（MPN）涂层的同源沸石咪唑骨架8（ZIF-8）纳米颗粒中。精心设计的纳米反应器可以同时破坏 pH 值和 H ₂ O ₂限制，并在照射下产生热疗，从而实现高效灭菌的三重CDT。此外，纳米反应器可以将CDT与光热疗法（PTT）和光动力疗法（PDT）相结合，不仅提高了杀菌效率，拓宽了抗菌谱，而且缓解了抗生素耐药问题。值得注意的是，所提出的纳米反应器实现了对革兰氏阳性耐甲氧西林金黄色葡萄球菌(MRSA) 和革兰氏阴性铜绿假单胞菌的强大体外细菌杀灭。纳米反应器在 MRSA 诱导的鼠脓肿模型中实现了 99.7% 的 MRSA 减少，且毒性可忽略不计。总体而言，本研究为多重增强 CDT 和多模式联合治疗病原体感染提供了一种有前景的策略。