自组装糖簇复合材料的构建及其多模式抗耐药菌研究

Drug-resistant bacteria which can easily form biofilms are a critical clinical problem that is very challenging to be solved. Pseudomonas aeruginosa (P. aeruginosa) is prone to forming biofilms that are resistant to external attacks, which has become one of the most common drug-resistant bacteria on wounds and in respiratory tract of clinical patients. In particular, P. aeruginosa infection poses a serious threat to patients with skin tissue injury or with damaged bone tissue. The use of antibiotics is the conventional way for treatment of bacterial infection. However, the overuse of antibiotics can lead to bacterial resistance, variability and other clinical problems. As a result, the development of alternative antibacterial tools for effective killing of drug-resistant bacteria is of urgent need. With this project we aim to construct an glycomaterial based on two-dimensional materials for multimodal treatment of drug-resistant bacteria. The glycomaterials formed by a one-step self-assembly can target P. aeruginosa through multivalent interaction with its surface-protein, LecA and LecB. Subsequently, near-infrared-light-driven photothermal combined with white-light-driven ROS production significantly degrades the biofilm formed by P. aeruginosa in vitro. This would thus set the basis for the treatment of P. aeruginosa infection on wounds and for bone repair in vivo. Our strategy provide a new tool for the treatment of P. aeruginosa infection on chronic wounds and for bone-repair materials in vivo.

易形成生物被膜的耐药菌是目前临床需要解决的棘手问题，绿脓杆菌凭借其易形成生物被膜顽固地抵御外界的攻击，已是临床患者伤口及呼吸道感染的常见耐药菌之一，尤其针对体外皮肤组织及骨组织损伤的患者感染严重，治疗中抗生素经常成为必选的药物。然而，研究发现抗生素过量使用会带来细菌耐药性、变异性等临床问题。本项目拟构建一种新型具备优异光学性能的糖簇复合纳米材料，借助糖簇能够特异性靶向绿脓杆菌表面糖结合蛋白LecA/LecB，同时二维纳米材料的光学性能促进其生物被膜的降解，从而针对体外及活体表皮伤口组织感染的绿脓杆菌，实现靶向标记及在光驱动条件下的热驱动协同自由基抑菌效果，进一步将复合纳米材料应用于骨修复材料上，实现骨修复材料具备体内抗菌效果，最终抑制绿脓杆菌的体内外感染，为抵御体外、活体表皮伤口乃至体内骨修复材料上感染的绿脓杆菌提供一种新型有效的“诊疗一体化”工具。

本项目针对临床抗生素滥用引发的耐药性、变异性等问题，通过在卟啉分子结构上修饰糖基化合物基团，借助糖基化合物能够特异性靶向细菌表面的结合蛋白LecA/LecB，进而促进复合纳米材料与细菌的黏附，最终通过卟啉化合物在660 nm光照条件下释放自由基性能，同时石墨烯纳米带材料在808 nm光照条件下释放热性能，针对体外及活体表皮伤口组织感染的绿脓杆菌，光驱动条件下实现热驱动协同自由基杀菌和根除细菌形成的生物被膜效果。研究中巧妙地设计了将荧光标记、生物靶向、生物相容多种优良性能融合于一体的新型卟啉类荧光探针，与结构可控且具备优异光学性能的石墨烯纳米带材料复合构建成多模式的抗菌材料，期待发展成为基于石墨烯纳米带的靶向诊疗细菌材料。同时，本项目构建的复合材料也为临床耐药菌的诊断和治疗提供了一种新的化学工具。