Precise Localization and Simultaneous Bacterial Eradication of Biofilms Based on Nanocontainers with Successive Responsive Property toward pH and ATP.

Abstract

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 (Ni2+, Zn2+, and Cu2+) 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 via 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.