葫芦[8]脲介导的四氧化三铁纳米酶-葡萄糖氧化酶核壳型杂化酶的构建及其抗细菌感染性能研究

Infectious diseases caused by bacteria have been one of the severely increasing healthy problems. There is a large demand to explore innovative materials for effectively bacteria killing and biofilm eradication. Fe3O4 nanoparticles with peroxidase-like activity could catalyze H2O2 into hydroxyl radical (•OH) with more potent antibacterial activity. However, the concentrations of H2O2 used with Fe3O4 nanozyme are higher than physiological levels, limiting its further application in vivo. This proposal focused on the modification of Fe3O4 nanozyme with in situ generation of H2O2 for smart bacteria killing. We plan to modify the surface of Fe3O4 nanoparticles with layer by layer self-assembled multilayer films of cucurbit[8]uril-based positively charged polymers and glucose oxidase. The highly loaded glucose oxidase can convert glucose abounding in biofilm into concertrated H2O2. The stimuli-responsive cucurbit[8]uril-based positively charged polymers can induce the disassembly of the glucose oxidase films, promoting the released naked Fe3O4 nanozyme to catalyze H2O2 into •OH. The efficiency of loading glucose oxidase and its production of H2O2, and the controlled catalyzing activity of Fe3O4 nanoparticles will be discussed in detail. The combined enzyme system will be explored in its antibacterial properties and the effect of breaking down biofilms both in vito and in vivo. This system will provide a new strategy for treatment of bacterial infections.

细菌感染是当前对人类健康最具威胁性的疾病之一，迫切需要研发新型抗菌材料以克服生物膜耐药性和高效杀菌。四氧化三铁纳米粒子具有类似过氧化物酶的性质，能够催化过氧化氢生成高抗菌活性的羟基自由基，因而是一种优良的抗菌材料。然而，四氧化三铁纳米酶催化反应需要较高浓度的过氧化氢，限制了其在体内的进一步应用。本项目通过在四氧化三铁纳米粒子表面层层自组装基于葫芦[8]脲的阳离子性超分子聚合物/葡萄糖氧化酶多层膜，利用大量负载的葡萄糖氧化酶在细菌生长的葡萄糖环境自发提供过氧化氢，利用葫芦[8]脲复合物的动态可逆性实现四氧化三铁纳米酶的可控释放，继而发挥高效的催化作用。探索构建葡萄糖氧化酶-四氧化三铁过氧化物酶级联催化体系，实现细菌生长环境中的葡萄糖向羟基自由基的转化，发挥杀菌和降解生物膜的作用，为细菌感染的治疗提供新的策略。

细菌感染是当前对人类健康最具威胁性的疾病之一，迫切需要研发新型抗菌材料，以克服生物膜耐药性和高效杀菌。本项目的资助下，我们围绕新型纳米酶抗菌材料这一研究目标，在四氧化三铁过氧化物纳米酶表面静电负载葡萄糖氧化酶涂层，构建了核壳型杂化酶组装体，此制备技术可实现对葡萄糖氧化酶的可控负载。在葡萄糖存在下，杂化酶可产生大量过氧化氢底物，继而发挥过氧化物酶活性催化产生羟基自由基。此杂化酶体系在细菌生长的葡萄糖环境中，催化葡萄糖生成羟基自由基，进而发挥高效的杀菌和抑制生物膜的作用，动物实验证明其能抑制炎症反应，有效促进细菌感染伤口的愈合，为细菌感染的防治提供了一种新的手段。.以此研究为基础，进一步开发了更加高效的纳米酶材料，1）突破了酸性pH条件的限制，构建了中性生理条件时发挥高效杀菌作用的铜基纳米酶。2）开发了一种硫铁矿纳米酶，其具有GSH氧化物酶-过氧化物酶双酶活性，能发挥级联自催化效应，是一种良好的抗肿瘤材料。.