基于细菌生物被膜结构特征构建生物学自适应抗菌高分子材料

Resistance has developed virtually to every class of antibiotics in current use. The emergence of drug resistance pathogens is an increasingly significant global economic and healthcare crisis. In the face of rising concerns over the development of antibiotic resistance, antibiotic clinical treatment strategies may not be adequate to combat the problem. It is necessary to develop new effective non-antibiotic drug to address resistance. In allusion to resistance mechanism of bacteria, the project is planning to design and prepare self-adaptive and specific recognition materials. According to the resistance mechanism and the specific microenvironment of bacterial infection, we use controllable active polymerization and self-assembly technology to synthesize the polymers that possess the properties of response to the infection microenvironment, high targeting and multi-targeting sites. By introducing the effective dose of antibacterial group with light-sensitivity, glycosyl molecules with specific recognition, the project will study the effect of the material structure on antibacterial activity, and further explore the influence of the material chemical and physical properties on their antibacterial effect to obtain the basic law of the antibacterial materials prepared. This project will choose pseudomonas aeruginosa lung infection in rats to study the distribution, recognition and antibacterial efficacy of the materials in vivo. The project can systematically reveal the antimicrobial mechanism of materials from the molecule, cell and whole hierarchy levels, which will provide the helpful information for bacterial infection therapy. Additionally, if a new effective antibacterial drug with avoiding resistance is obtained, the project will offer important experiment data and scientific basis for the development of antimicrobial drug and the exploration of new treatment method.

抗生素的泛用和滥用致使细菌耐药的问题日趋恶化，严重威胁人类的健康，迫切需要发展新型、高效的非抗生素药物。针对细菌耐药这一问题，依据细菌生物被膜结构特征和细菌感染微环境生物学特性，本项目通过聚合物的分子设计、可控活性聚合和纳米组装技术等设计理念和方法，拟构建具有高亲和性和响应细菌感染微环境的功能抗菌高分子材料；通过引入有效剂量的特异性识别分子和抗菌基团，系统研究材料结构与尺度因素对高亲和性、环境响应性及抗菌活性的影响；进一步研究抗菌材料的理化性质与其抗生物被膜效应的关系，探寻材料设计的基本规律；建立铜绿假单胞菌感染小鼠肺部模型，研究抗菌材料进入体内的治疗效果和可能的副作用。从分子、细胞和整体层次上系统揭示材料的作用机制。新型非抗生素药物一旦研制成功，不但避免细菌耐药性的发生，还可为全新、安全、方便细菌感染疾病治疗药物开发和治疗新方法的探索提供重要的实验数据和科学依据。

抗生素的泛用和滥用致使细菌耐药的问题日趋恶化，严重威胁人类的健康，迫切需要发展新型、高效的非抗生素药物。针对细菌耐药这一问题，依据细菌生物被膜结构特征和细菌感染微环境生物学特性，本项目通过聚合物的分子设计、可控活性聚合和纳米组装技术等设计理念和方法，拟构建具有高亲和性和细菌感染微环境响应性的功能抗菌高分子材料；通过引入有效剂量的特异性识别分子和抗菌基团，系统研究材料结构与尺度因素对高亲和性、细菌感染微环境响应性及抗菌活性的影响；进一步研究抗菌材料的理化性质与其抗生物被膜效应的关系，探寻材料设计的基本规律；建立铜绿假单胞菌感染小鼠肺部模型，研究抗菌材料进入体内的治疗效果和可能的副作用。从分子、细胞和整体层次上系统揭示材料的作用机制。新型非抗生素药物的研制，不但避免细菌耐药性的发生，还可为全新、安全、方便细菌感染疾病治疗药物开发和治疗新方法的探索提供重要的实验数据和科学依据。