多功能银/抗生素协同纳米载体的构建及主动靶向杀灭布鲁氏菌的新策略研究

Brucellosis caused by Brucella is a zoonotic infectious disease that possesses serious threats to animal husbandry, human health and public health security．Therefore, it is of great significance to develop the new strategy for effective killing Brucella. The project is based on the design, synthesis to application as the study idea, easy endocytosis of nanoparticles by macrophages as the key point and Brucella in macrophages as the object of the research to construct novel dumbbell-like asymmetrical nanocarriers for active-targeted killing Brucella in infected macrophages. The effect of targeted killing Brucella in the infected macrophages and mice using nanocarriers with combined silver nanoparticle/antibiotic will be systematically studied and the mechanism of the synergistic killing bacteria will be discussed. The research method can be extended to kill active-targetedly other disease-causing bacteria such as Y. pestist, F. tularens, M. tuberculosis in order to construct a series of nanocarriers for killing bacteria. Through the implementation of this project, the new strategy for active-targeted killing Brucella can be established based on silver/antibiotic synergistic effect using novel asymmetrical nanocarriers, which further promotes the application of asymmetrical nanomaterials for killing the disease-causing bacteria in macrophages.

布鲁氏菌病是由布鲁氏菌引起的人、畜共患传染病，对畜牧业、人类健康和社会公共卫生安全构成重大威胁，因此开发有效杀灭布鲁氏菌的新策略具有重要的意义。项目以“设计-合成-应用”为研究思路，以纳米粒子易于被巨噬细胞吞噬及为着眼点，以寄生在巨噬细胞里的布鲁氏菌为研究对象，致力于构建主动靶向杀灭寄生在巨噬细胞里的致病细菌的新型哑铃形非对称性纳米载体，系统研究其在布鲁氏菌感染的巨噬细胞和小鼠体内的主动靶向银纳米粒子/抗生素协同杀菌的效果，探讨其协同作用杀菌的机制。研究方法可拓展到主动靶向杀灭寄生在巨噬细胞里的其它致病细菌（如鼠疫杆菌、土拉弗朗西斯菌及结核杆菌），构建出系列多功能杀菌纳米载体。通过本项目的实施，可建立基于银/抗生素协同的新型非对称纳米载体对主动靶向杀灭布鲁氏菌的新策略，推动不对称纳米材料在杀灭寄生在巨噬细胞里的致病细菌的应用发展。

微生物感染是当今科学家们尝试攻克的难题之一，对人类健康和社会公共卫生安全构成重大威胁，抗生素的到来虽给予了人们希望，但随之而来的耐药性使抗生素的使用受到限制。因此开发有效杀灭细菌的新策略具有重要的意义。项目以“设计-合成-应用”为研究思路，以纳米粒子安全、高效、广谱为着眼点，以多种常见细菌为研究对象，致力于构建主动靶向快速杀灭细菌的新型非对称性纳米载体，系统研究其离子抗菌、抗菌剂抗菌、光热抗菌以及光动力抗菌等协同杀菌的效果，探讨其协同作用杀菌的机制，达到“小杠杆撬动大成效”的目的。通过本项目的实施，可建立基于新型非对称纳米载体抑菌的新策略，推动不对称纳米材料在抑菌领域的应用发展。