Key Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University) Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China.
State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, CAS, Beijing 100085, China.
Acta Biomater. 2023 Jul 1;164:487-495. doi: 10.1016/j.actbio.2023.04.009. Epub 2023 Apr 14.
Accurate and sensitive detection of bacteria is essential for treating bacterial infections. Herein, a pH-responsive magnetic resonance tuning (MRET) probe, whose T-weighted signal is activated in the bacteria-infected acid microenvironment, is developed for in situ accurately magnetic resonance imaging (MRI) of bacterial infection in vivo. The MRET probe (MDVG-1) is an assembly of paramagnetic enhancer (gadolinium-modified i-motif DNA, abbreviated as Gd-DNA-Gd) and the precursor of superparamagnetic quencher (DNA and vancomycin-modified magnetic nanoparticle, abbreviated as MDV). The T-weighted signal of Gd-DNA-Gd is quenched once the formation of MDVG-1 (MRET ON). Interestingly, the MDVG-1 probe was disassembled into the monomers of Gd-DNA-Gd and MDV under the bacteria-infected acid microenvironment, resulting significantly enhanced T-weighted signal at the infected site (MRET OFF). The pH-responsive MRET probe-based enhanced MRI signal and bacteria targeting significantly improve the distinction between bacterial infectious tissues and sterile inflamed tissues, which provides a promising approach for accurately detecting bacterial infection in vivo. STATEMENT OF SIGNIFICANCE: Detecting pathogenic bacteria in vivo based on magnetic resonance imaging (MRI) strategy has been exploring recently. Although various bacterial-targeted MRI probes have been developed to image bacteria in vivo, the MRI signal of these MRI probes is always "on", which inevitably generates nonspecific background MRI signals, affecting the accuracy of MRI to a certain extent. In the current study, based on the magnetic resonance tuning (MRET) phenomenon, we present a pH-responsive MRET probe (MDVG-1) with T-weighted imaging to T-weighted imaging switchable properties to achieve in situ precise imaging of bacterial infection in vivo.
准确灵敏的细菌检测对于治疗细菌感染至关重要。在此，开发了一种对细菌感染酸性微环境具有响应性的磁共振调谐（MRET）探针，该探针的 T 加权信号在细菌感染的酸性微环境中被激活，可用于体内细菌感染的原位磁共振成像（MRI）。该 MRET 探针（MDVG-1）由顺磁增强剂（钆修饰的 i-motif DNA，简称 Gd-DNA-Gd）和超顺磁猝灭剂的前体（DNA 和万古霉素修饰的磁性纳米颗粒，简称 MDV）组成。一旦形成 MDVG-1（MRET ON），Gd-DNA-Gd 的 T 加权信号就会被猝灭。有趣的是，在细菌感染的酸性微环境下，MDVG-1 探针会分解成 Gd-DNA-Gd 和 MDV 的单体，从而导致感染部位的 T 加权信号显著增强（MRET OFF）。基于 pH 响应的 MRET 探针的增强 MRI 信号和细菌靶向性显著提高了细菌感染组织和无菌性炎症组织之间的区分度，为体内准确检测细菌感染提供了一种很有前途的方法。
基于磁共振成像（MRI）策略的体内致病性细菌检测最近受到了广泛关注。尽管已经开发了各种细菌靶向 MRI 探针来对体内细菌进行成像，但这些 MRI 探针的 MRI 信号始终处于“开”状态，这不可避免地会产生非特异性的背景 MRI 信号，在一定程度上影响 MRI 的准确性。在本研究中，基于磁共振调谐（MRET）现象，我们提出了一种 pH 响应的 MRET 探针（MDVG-1），该探针具有 T 加权成像到 T 加权成像开关的特性，可实现体内细菌感染的原位精确成像。
