Rapid and selective tumor detection using conventional pH-activatable chemical probes as contrast agents is challenging. Moreover, a large proportion of the contrast agent is usually retained in the body long-term, which causes potential toxicity risks. In this study, we developed a fluorescent sensor, CypH2S, with a pH-sensitive cyclic substructure for detection of acidic tumor microenvironment. Upon pH variation, the sensor underwent structural changes: the closed-ring form, CypH2S-C, exhibited suppressed dye aggregation, while the open-ring form, CypH2S-O, tended to aggregate in aqueous solutions under slightly acidic conditions. Importantly, CypH2S facilitated rapid and selective tumor visualization in a living mouse model via fluorescence imaging of its pH-responsive aggregation with a 1.9-fold tumor/background ratio (< 1 h). Furthermore, prompt clearance of CypH2S from the bloodstream post-tumor detection occurred because of the relatively small size of the aggregates and cell impermeability. These properties would make CypH2S a promising candidate for clinical tumor diagnosis.

中文翻译：

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使用快速清除的花青染料的 pH 响应性聚集进行快速肿瘤成像

使用传统 pH 激活化学探针作为造影剂进行快速、选择性肿瘤检测具有挑战性。而且，大部分造影剂通常会长期滞留在体内，造成潜在的毒性风险。在这项研究中，我们开发了一种荧光传感器 CypH2S，具有 pH 敏感的循环子结构，用于检测酸性肿瘤微环境。 pH 变化时，传感器发生结构变化：闭环形式 CypH2S-C 表现出抑制的染料聚集，而开环形式 CypH2S-O 在微酸性条件下的水溶液中倾向于聚集。重要的是，CypH2S 通过其 pH 响应聚集的荧光成像，肿瘤/背景比为 1.9 倍（< 1 小时），从而促进了活体小鼠模型中快速、选择性的肿瘤可视化。此外，由于聚集体尺寸相对较小且细胞不渗透性，肿瘤检测后 CypH2S 从血流中迅速清除。这些特性将使 CypH2S 成为临床肿瘤诊断的有希望的候选者。