AgNPs/FcSB壳聚糖水凝胶通过干扰细菌QS系统治疗生物膜相关感染

细菌生物膜（BBF）耐药性极强，能够抵御和逃避宿主的免疫效应，是导致许多顽固性感染的重要原因。随着植入性医疗器械的广泛应用，细菌生物膜相关感染 (BAI) 的发病率日益增高，已成为医学界亟待解决的重大难题。开发新型抗菌材料从根本上阻断BBF的形成是治疗BAI的关键。在前期研究验中，我们发现并验证了几种二茂铁-碳硼烷衍生物（FcSB）具有优良的抗菌抗感染效果。本项目拟在前期研究基础上采用FcSB作为主要抗菌活性分子，用具有持久抗菌效果的纳米银包被FcSB，再通过壳聚糖进行交联，制备成一种非抗生素型纳米抗菌凝胶医用材料 (ACVCSG)。通过评价ACVCSG的体内外抗菌、抗BBF的效果；验证其对细菌LuxS/AI-2型QS系统信号分子的可能抑制作用及对相关基因和蛋白表达的影响，进而阐明其治疗BAI的药物靶点和作用机制，为临床靶向治疗BAI这一医学难题提供新的解决方案和理论基础。

Bacterial biofilm (BBF) is one of the main reasons caused many refractory infections, because it has a high resistance to the traditional antibiotics and be able to resist and evade the host immune response. With the widely application of implantable medical devices, the rising mobidity of the biofilm-associated infections (BAI) has been a major issue urgently to be solved in the medical profession. So developing new type of antibacterial materials to block the formation of BBF is the key to the fundamentally treatments. In previous reports, we have found some of ferrocene-carborane derivatives (FcSB) have excellent antibacterial and anti-infection effects. Based on the previous work, we intend to prepare a non-antibiotic antimicrobial nano medical hydrogel materials (ACVCSG) by crosslinking the main active molecules (FcSB) and the AgNPs which have persistent antibacterial effect with chitosan. We explore the antibacterial and anti-biofilm properties of the ACVCSG in vitro and in vivo；the inhibitory effect to the bacterial LuxS/AI-2-dependent quorum-sensing (QS) system and the impact to the expression quantity of the related genes and proteins. Thus, we illustrate the target sites and the mechanism of the ACVCSG treating BAI. This research will provid the theory basis and a new avenue for the targeting therapy of BAI.