CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, China.
Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, China.
Angew Chem Int Ed Engl. 2021 Jun 25;60(27):14887-14891. doi: 10.1002/anie.202104408. Epub 2021 May 26.
The dynamic variation of the expression profile and spatial landscape of multiple enzymes are crucial factors influencing tumor progression and drug treatment. However, the comprehensive analysis of these events has been hampered by the limitations of existing imaging technologies. Here we report a cooperatively activatable, DNA-based fluorescent reporter programmed to detect the correlated activity of dual enzymes, telomerase (TE) and apurinic/apyrimidinic endonuclease 1 (APE1), both in vitro and in vivo. The conformational change of the DNA probe can be orthogonally triggered through TE-induced DNA elongation and APE1-mediated specific cleavage, producing a fluorescent signal for imaging the activity of the two enzymes in an AND-gated manner. Furthermore, we demonstrate the capability of the system for specific tumor imaging through "dual lock-and-key" strategy, and visualizing the correlated enzymatic activities during drug treatment of cancer.
多种酶的表达谱和空间景观的动态变化是影响肿瘤进展和药物治疗的关键因素。然而，这些事件的综合分析受到现有成像技术的限制。在这里，我们报告了一种协同激活的基于 DNA 的荧光报告基因，该报告基因被编程用于体外和体内检测端粒酶 (TE) 和脱嘌呤/脱嘧啶内切酶 1 (APE1) 两种酶的相关活性。DNA 探针的构象变化可以通过 TE 诱导的 DNA 延伸和 APE1 介导的特异性切割正交触发，产生荧光信号，以 AND 门方式对两种酶的活性进行成像。此外，我们通过“双重锁钥”策略证明了该系统用于特定肿瘤成像的能力，并在癌症的药物治疗过程中观察到相关酶活性。
