多功能磁性纳米药物载体复合物的构建及其抗口腔细菌生物膜作用研究

Oral bacterial biofilms exhibit high pathogenicity and drug-resistance. How to eradicate biofilms is a great challenge for oral infectious diseases control and treatment. Oral biofilms often hide in places hardly for drugs to reach, and it is also difficult for drugs to penetrate into biofilms with matrix barrier. That is why many antibacterial drugs can not eradicate biofilms. So, it needs to find an ideal drug delivery system, which is effective and safe to transport drugs into biofilms and then to release drugs against bacteria living inside biofilms, thus destroying the entire structure. Our research team has already successfully loaded a novel magnetic nano-drug carrier with antitumor drugs. On the basis of previous work, we plan to synthesize a multifunctional magnetic nano-drug carrier composite containing antibacterial drugs and DNA enzyme in this project. Drugs can be guided to penetrate tissues and biofilm matrix barriers in the magnetic field, diffusing into biofilms rapidly and killing bacteria inside. Moreover, a dual controlled release system sensitive to both pH and temperature will be designed, forming effective antibacterial concentration inside biofilms with less cytotoxicity to surrounding tissues. The result may suggest the appropriate antibacterial drugs and antibiofilm conditions for the synthesis of the antibiofilm multifunctional magnetic nano-drug carriers, as well as provide ideas for developing a more efficient and safer antibiofilm drug delivery system in future.

口腔细菌生物膜致病性强，耐药性高，如何有效清除生物膜是防治口腔感染性疾病面临的挑战。生物膜常形成于药物难以抵达的隐匿部位，生物膜基质屏障又能阻挡药物渗入，这是许多抗菌药物无法破坏生物膜的重要原因。所以，我们需要寻找一种高效且安全的理想药物释放系统，能将药物靶向运输入生物膜内部，再通过激活释放药物，从生物膜内部有效杀灭细菌，破坏生物膜整体结构。在本项目组前期成功利用新型磁性纳米药物载体负载抗肿瘤药物的基础上，本项目拟构建负载抗菌药物与DNA酶的多功能磁性纳米药物载体复合物，借助外磁场力靶向引导药物穿透组织，突破生物膜屏障，更快渗入生物膜内杀灭细菌。同时，采用pH值/温度双重控释系统，使药物在生物膜内部达到有效抗菌浓度，并减少对周围组织毒性。本研究结果有利于为构建负载抗生物膜药物的多功能磁性纳米载体筛选合适的负载药物与抗生物膜条件，也为今后发展一种更有效、安全的抗生物膜药物释放系统提供思路。

在口腔组织深处，如牙面深窝沟、根管内、牙周袋内的牙菌斑生物膜是临床上造成多种口腔疾病迁延不愈的主要原因。而生物膜独特的三维结构与基质屏障使现有的抗生素难以有效地发挥抗菌作用。本研究构建了一种具有顺磁性与对pH值/温度双重敏感特点的多功能磁性纳米载药复合物，其在外磁场的引导下可靶向穿透生物膜，同时在生物膜内部特定的pH值/温度环境下控释药物，于局部达到有效的药物浓度，从内部破坏生物膜的结构，且可减少对周围正常组织的毒性作用。本研究为口腔组织深部由牙菌斑生物膜引发的口腔疾病的防治提供了新的思路，也具有对其它深部结构的感染性疾病精准治疗的应用前景。