光驱动降解绿脓杆菌生物被膜的二维糖簇材料构建

Pseudomonas aeruginosa (P. aeruginosa) exist as the most common gram negative bacterium clinically, and is infectious and strongly drug-resistant. In particular, the biofilms formed by P. aeruginosa on respirators and operating tables can cause a high infectious, and thus death rate of patients with low immunity. Aiming to overcome the difficulty in treating free P. aeruginosa and its biofilms, we construct a new type of graphene-like glyco-materials based on the biocompatible two-dimensional (2D) molybdenum disulfide and manganese dioxide. The material composite is formed by a one-pot self-assembly facilitated by strain-promoted click chemistry and thiol-material adsorption, capable of encapsulating antibiotics. The 2D glyco-materials will be used to target the carbohydrate-binding proteins on the surface of P. aeruginosa, thereby releasing the drugs and reactive oxygen species by near-infrared and white light irradiation, respectively. In addition to killing free P. aeruginosa, the materials will be used to degrade the P. aeruginosa biofilms formed on clinical instruments, offering new insights into the treatment of bacteria biofilms, which represent an intractable problem clinically.

绿脓杆菌是目前临床最为常见的格兰氏阴性菌之一，具有很强的人感染能力且易产生耐药性，尤其在医院常规医疗器械如呼吸机、手术台等材质表面易形成顽固的绿脓杆菌生物被膜，从而对抵抗力低下的病患造成高感染风险与高致死率。针对现有抗生素与消毒剂几乎无法降解绿脓杆菌生物被膜的关键问题，本项目拟构建一种新型基于高生物相容度、具备优异光学性能二维硫化钼和二维氧化锰的糖簇抗菌材料，通过简洁的环应力点击化学与巯基表面吸附“一步法”自组装策略，高效构建可包裹抗生素的材料复合体。随即通过糖簇对绿脓杆菌表面糖结合蛋白的特异性靶向，实现在近红外光辐射下的热驱动释药和白光辐射下的自由基杀菌。除对游离绿脓杆菌进行联合光驱动抑菌外，还尝试将二维糖簇抗菌材料应用于临床医疗器械上绿脓杆菌生物被膜的光驱动降解，为此类顽固细菌提供新的治疗工具。

细菌感染是普遍存在的问题，绿脓杆菌已是临床患者伤口感染的常见耐药菌之一，尤其针对体外皮肤组织损伤的患者感染严重，治疗中抗生素成为必选的疗法。然而研究发现抗生素的过量使用引发了细菌耐药性、变异性等临床问题。同时，抗生素并不能有效降解绿脓杆菌等耐药菌形成的生物被膜。于是，本项目通过构建基于二维纳米材料二硫化钼与糖基化合物自组装的复合纳米材料，利用复合纳米材料的载药性能，包载抗生素，得到携带抗生素的复合纳米材料。借助二硫化钼纳米材料在近红外光（808 nm）和白光（400-700 nm）照射条件下分别能够释放热和自由基的性能，同时糖基化合物能够特异性靶向绿脓杆菌表面糖结合蛋白LecA/LecB，最终实现了协同抗生素彻底抑菌及降解生物被膜效果，有效避免了抗生素的滥用，为耐药菌防治领域提供了新的有潜在临床应用价值的化学工具。