Development of functional anti-cancer molecules based on precise control of excitation and relaxation pathways

发展具有足够特异性和灵敏度的肿瘤成像技术是癌症诊断的长期目标。为了实现这一目标，最小化源自非靶组织的背景信号是至关重要的。在这里，我们通过采用新设计的靶向“可激活”荧光成像探针实现了高度特异性的体内癌症可视化。该试剂在细胞内化后通过感测溶酶体中的pH变化而被激活。合成了基于BODIPY荧光团的新型酸性pH可激活探针，然后将其与靶向癌症的单克隆抗体缀合。作为概念证明，进行小鼠中HER2阳性肺癌细胞的体外和体内成像。该探针对肿瘤具有高度特异性，背景信号最小。

It is a long-term goal of cancer diagnosis to develop tumor-imaging techniques that have sufficient specificity and sensitivity. To achieve this goal, minimizing the background signal originating from non-target tissues is critical. Here, we achieve highly specific in vivo cancer visualization by employing a newly-designed targeted "activatable" fluorescent imaging probe. This agent is activated after cellular internalization by sensing the pH change in the lysosome. Novel acidic pH-activatable probes based on the BODIPY fluorophore were synthesized, and then conjugated to a cancer-targeting monoclonal antibody. As proof of concept, ex and in vivo imaging of HER2-positive lung cancer cells in mice were performed. The probe was highly specific for tumors with minimal background signal.