Abstract：
Multidrug-resistant (MDR) bacteria-infected wound healing remains greatly challenging, especially in diabetic patients. Herein, a novel nano-drug delivery based on endogenous glucose-driven cascade reaction is proposed for boosting MDR bacteria-infected diabetic wound healing with high efficacy by improving wound microenvironment and enhancing photodynamic antibacterial activity. The composite nanoagent is first self-assembled by integrating berberine (BBR) and epigallocatechin gallate (EGCG) from natural plant extracts, named as BENPs, which is successively coated with manganese dioxide nanoshells (MnO2 NSs) and glucose oxidase (GOX) to form the final BEMGNPs. The cascade reaction is triggered by glucose at the wound site of diabetes which is specifically catalyzed by GOX in the BEMGNPs to produce gluconic acid and hydrogen peroxide (H2O2). That is subsequently to decompose MnO2 NSs in the BEMGNPs to generate oxygen (O2). The BEMGNPs as photosensitizers effectively produce reactive oxygen species (ROS) to enhance the eradication of bacteria with the assistance of O2. Under the synergistic function of the cascaded reaction, the BEMGNPs present excellent antibacterial efficacy even for MDR bacteria. The in vivo experiments explicitly validate that the constructed nano-drug delivery can augment the MDR bacteria-infected diabetic wound healing with excellent biosafety. The as-proposed strategy provides an instructive way to combat ever-threatening MDR bacteria, which particularly is beneficial for diabetic patients.
摘要：
多药耐药（MDR）细菌感染的伤口愈合仍然非常具有挑战性，尤其是糖尿病患者。在这里，提出了一种基于内源性葡萄糖驱动的级联反应的新型纳米药物递送，通过改善伤口微环境和增强光动力抗菌活性，以高效促进MDR细菌感染的糖尿病伤口愈合。复合纳米剂首先通过从天然植物提取物中整合小檗碱（BBR）和表没食子儿茶素没食子酸酯（EGCG）来自组装，命名为BENPs，依次用二氧化锰纳米壳(MnO2NS)和葡萄糖氧化酶(GOX)涂覆以形成最终的BEMGNP。级联反应由糖尿病伤口部位的葡萄糖触发,其由BEMGNP中的GOX特异性催化以产生葡糖酸和过氧化氢(H2O2)。随后分解BEMGNP中的MnO2NSs以产生氧(O2)。作为光敏剂的BEMGNP有效地产生活性氧(ROS)以在O2的帮助下增强细菌的根除。在级联反应的协同作用下，即使对于MDR细菌，BEMGNP也具有出色的抗菌功效。体内实验明确地验证了构建的纳米药物递送可以以优异的生物安全性增强MDR细菌感染的糖尿病伤口愈合。拟议的策略提供了一种有启发性的方法来对抗威胁性的MDR细菌，这对糖尿病患者尤其有益。
