Tunable Hierarchically Porous Gadolinium-Based Metal-Organic Frameworks for Bacteria-Targeting Magnetic Resonance Imaging and In Situ Anti-Bacterial Therapy.

Abstract

Currently, there are no non-invasive tools to accurately diagnose deep surgical site bacterial infections before they cause significant anatomical damage in the clinic. An urgent need exists for bacteria-targeting bifunctional probes for the detection of deep bacterial infections and precise in situ treatment. Herein, the bacteria-targeting 1-borono-3,5-benzenedicarboxylic acid (BBDC) ligand and paramagnetic Gd^3 + into one single metal-organic frameworks (MOFs) are integrated, synergistically realizing bacteria-specific magnetic resonance imaging (MRI) diagnosis and MRI-guided antibacterial treatment. Molecular simulations and nitrogen adsorption-desorption experiments demonstrate that a hierarchical porous structure can be constructed by tuning the Gd^{3 +} /BBDC ratio, which endows the Gd-BBDC1.25 MOFs with an impressive longitudinal proton relaxivity of 15.81 mM^-1 s^-1. In particular, the bacteria-targeting boronic acid group in BBDC remained intact during the MOF synthesis, ensuring that Gd-BBDC1.25 MOFs have a unique combination of high sensitivity and specificity for bacteria. Through an in situ reduction reaction, silver nanoparticles （Ag NPs）-modified Gd-BBDC1.25 MOFs to form Ag@Gd-BBDC1.25, an interfacial Schottky heterojunction nanozyme, which enhances their peroxidase (POD)-catalyze activity. Furthermore, it is demonstrated that the bacteria-targeting Ag@Gd-BBDC1.25 bifunctional probe can image as few as 10⁵ colony-forming units (cfu) in vivo and effectively eradicate the bacteria in situ.