Key Laboratory of Marine Environmental Corrosion and Bio-fouling, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China.
University of the Chinese Academy of Sciences, Beijing 100039, China.
ACS Appl Mater Interfaces. 2023 Feb 15;15(6):8424-8435. doi: 10.1021/acsami.2c22682. Epub 2023 Feb 6.
The bacterial colonization of surfaces and subsequent biofilm formation are a great threat in medical therapy and clinical diagnosis. The complex internal structure and composition sets an enormous obstacle for the localization and removal of biofilms. In this study, we proposed a novel biofilm-targeted nanocontainer with successive responsive property toward pH and ATP for precise localization and simultaneous bacterial eradication, with an acidic and adenosine triphosphate (ATP)-rich microenvironment within biofilms, formed due to the accumulation of fatty acids and ATP in the three-dimensional enclosed structure, integrated as two successive indicators to improve the precision of biofilm identification and removal. The biofilm-targeted nanocontainer was composed of a ATP-responsive zeolitic imidazolate framework-90 (ZIF-90) core loaded with Rho 6G and doxorubicin hydrochloride (DOX) encapsulated in the pH-responsive amorphous calcium carbonate/poly(acrylic acid) (ACC/PAA) shell. In the presence of biofilms, the ACC/PAA shell and ZIF-90 core were successively degraded by the accumulated H and ATP within biofilms, resulting in the release of fluorescence indicators and antimicrobial agents. On the other hand, to meet the application requirements of different biofilm scenarios, the pH response ability of the nanocontainers could be adjusted by changing the metallic ions (Ni, Zn, and Cu) doped into the structure of the ACC/PAA shell. Owing to excellent water dispersion of the pH/ATP double-responsive ZIF-90@Zn-ACC/PAA nanocontainer, precise localization and simultaneous bacterial eradication was successfully realized a simple spray process. The successive pH/ATP two-step unlocking processes endowed the nanocontainers high precision for localization and simultaneous eradication of biofilms, which made the proposed nanocontainers high promising in food safety and medical treatment.
表面细菌定植和随后生物膜的形成是医学治疗和临床诊断的巨大威胁。复杂的内部结构和组成给生物膜的定位和去除带来了巨大的障碍。在这项研究中，我们提出了一种新型的生物膜靶向纳米容器，具有 pH 和 ATP 连续响应特性，可实现精确的定位和同时的细菌清除，生物膜内形成酸性和三磷酸腺苷（ATP）丰富的微环境，这是由于三维封闭结构内脂肪酸和 ATP 的积累形成的，将其整合为两个连续的指标，以提高生物膜识别和去除的精度。生物膜靶向纳米容器由负载 Rho 6G 和盐酸多柔比星（DOX）的 ATP 响应沸石咪唑酯骨架-90（ZIF-90）核和封装在 pH 响应无定形碳酸钙/聚丙烯酸（ACC/PAA）壳中的纳米容器组成。在生物膜存在的情况下，ACC/PAA 壳和 ZIF-90 核被生物膜内积累的 H 和 ATP 依次降解，导致荧光指示剂和抗菌剂的释放。另一方面，为了满足不同生物膜场景的应用要求，可以通过改变掺杂到 ACC/PAA 壳结构中的金属离子（Ni、Zn 和 Cu）来调节纳米容器的 pH 响应能力。由于 pH/ATP 双响应 ZIF-90@Zn-ACC/PAA 纳米容器具有优异的水分散性，可以通过简单的喷涂工艺实现精确的定位和同时清除细菌。连续的 pH/ATP 两步解锁过程赋予纳米容器对生物膜的定位和同时清除的高精度，这使得所提出的纳米容器在食品安全和医疗方面具有很高的应用前景。
