Yu Youyi, Cui Tianming, Liu Chang, Yang Weitao, Zhang Bingbo
Department of Radiology, Tongji Hospital, Shanghai Frontiers Science Center of Nanocatalytic Medicine, the Institute for Biomedical Engineering & Nano Science, School of Medicine, Tongji University, Shanghai, 200065, China.
Shanghai Research Institute for Intelligent Autonomous Systems, Tongji University, Shanghai, 200065, China.
Adv Sci (Weinh). 2025 Apr;12(15):e2415209. doi: 10.1002/advs.202415209. Epub 2025 Feb 20.
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 Gdinto 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 /BBDC ratio, which endows the Gd-BBDC1.25 MOFs with an impressive longitudinal proton relaxivity of 15.81 mM s. 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 10 colony-forming units (cfu) in vivo and effectively eradicate the bacteria in situ.
目前，临床上尚无在深部手术部位细菌感染造成严重解剖学损伤之前进行准确诊断的非侵入性工具。迫切需要用于检测深部细菌感染和精确原位治疗的靶向细菌双功能探针。在此，将靶向细菌的1-硼酰基-3,5-苯二甲酸（BBDC）配体和顺磁性钆整合到单个金属有机框架（MOF）中，协同实现细菌特异性磁共振成像（MRI）诊断和MRI引导的抗菌治疗。分子模拟和氮气吸附-解吸实验表明，通过调节钆/BBDC比例可以构建分级多孔结构，这赋予Gd-BBDC1.25 MOF高达15.81 mM s的纵向质子弛豫率。特别地，BBDC中靶向细菌的硼酸基团在MOF合成过程中保持完整，确保Gd-BBDC1.25 MOF对细菌具有高灵敏度和特异性的独特组合。通过原位还原反应，银纳米颗粒（Ag NPs）修饰Gd-BBDC1.25 MOF形成Ag@Gd-BBDC1.25，一种界面肖特基异质结纳米酶，增强其过氧化物酶（POD）催化活性。此外，已证明靶向细菌的Ag@Gd-BBDC1.25双功能探针在体内能够对低至10个菌落形成单位（cfu）进行成像，并能有效原位根除细菌。
