Abstract：
Fluorescent nanosensor-based tumor imaging holds great promise in cancer diagnosis and treatment assistance, yet the signal contrast is heavily hampered by the unspecific/unwanted activation at microscopic regions with a highly restricted local abundance of biomarkers. Herein, we developed an activation boosting strategy by the integration and manipulation of dual-factor coactivation of sensing and lysosome escape facilitated the rise of cytosolic biomarker accessibility. By employing hybrid DNA probes on gold nanoquenchers, ATP sensing initiated conformation switch of the corresponding aptamer units triggered the exposure of a hidden toehold in a loop structure. Sequentially, miRNA-21 sensing was triggered by toehold-mediated strand displacement and detachment of the binding complexes. The application of lysosomotropic agent chloroquine at optimized time interval facilitated the release of nanosensors into the cytosol and a ∼10.5-fold increment of intracellular fluorescence in vitro, while coactivation improved the cancer-to-normal cell signal ratio by ∼5.9 times. The synergy effects led to a high tumor-to-normal tissue ratio value of ∼7.9 in the in vivo imaging results. This strategy establishes a new paradigm of fluorescent nanosensors for selective and specific tumor imaging.
摘要：
基于荧光纳米传感器的肿瘤成像在癌症诊断和治疗援助中具有巨大的前景，然而,在具有高度受限的局部生物标志物丰度的微观区域,非特异性/不需要的激活严重阻碍了信号对比.在这里，我们通过整合和操纵传感和溶酶体逃逸的双因素共激活促进了细胞溶质生物标志物可及性的提高,开发了激活增强策略.通过在金纳米猝灭剂上使用杂交DNA探针，ATP感测引发的相应适体单元的构象转换触发了环结构中隐藏的足托的暴露。按顺序,miRNA-21的传感是由支点介导的链置换和结合复合物的分离触发的。在优化的时间间隔内应用溶酶体促生长剂氯喹促进了纳米传感器释放到细胞质中，并在体外增加了细胞内荧光的约10.5倍，而共激活将癌细胞与正常细胞的信号比提高了5.9倍。协同作用导致体内成像结果中肿瘤与正常组织的比值高达7.9。该策略建立了用于选择性和特异性肿瘤成像的荧光纳米传感器的新范例。
