“双钥匙-单锁”近红外G-四链体荧光探针的构建及其在乏氧环境下对癌细胞和肿瘤中G-四链体DNA的“精准”成像研究

G-四链体 DNA（G4 DNA）是由富含串联重复鸟嘌呤（G）的DNA折叠所形成的高级结构，广泛存在于原癌基因启动子区域和端粒末端。从分子水平上“精准”示踪肿瘤环境中G4 DNA的生命活动规律，能为疾病诊断、生物医学研究提供非常有价值的信息。虽然最近开发的少数几种荧光探针可以用于检测活细胞中的G4 DNA，但是它们无法实现G4 DNA在癌细胞中的“精准”识别以及在活体层面的检测。本项目拟在传统G4荧光探针的分子结构上安装对肿瘤环境特异性响应的乏氧“识别”单元，构建一种基于G4 DNA与乏氧协同激活的“双钥匙-单锁”近红外G4荧光探针，从而实现肿瘤环境中G4 DNA的“精准”成像。利用探针“精准”获取乏氧环境下癌细胞和肿瘤中G4 DNA结构的形成、稳定性以及动态变化等信息，以期对致癌机理提供全新的见解，从而为发展基于G4 DNA为靶点的抗癌药物提供重要的理论指导和实践依据。

G-quadruplex DNA (G4 DNA) is an advanced structure formed by the folding of tandem repeat-rich guanine (G)-rich DNA, which is widely present in the promoter region and telomere ends of proto-oncogenes. It can provide very valuable information for disease diagnosis and biomedical research by “precise” tracking the laws of G4 DNA life activity in the tumor environment at the molecular level. A few of fluorescent probes have been developed recently that can be employed to examine G4 DNA in living cells, while they cannot achieve the “precise” recognition of G4 DNA in cancer cells and the detection at the living level. By installing a hypoxic “recognition” unit specific to the tumor environment on the molecular structure of a conventional G4 fluorescent probe, this project intends to build a “dual-key-single-lock” near-infrared G4 fluorescent probe based on the synergistic activation of G4 DNA and hypoxia for “precise” imaging of G4 DNA in the tumor environment. Using probes to obtain information “accurately” about the formation, stability, dynamic changes of G4 DNA structures in cancer cells and tumors under hypoxic environment, and then to provide new insights into carcinogenic mechanisms, and thus to provide important theoretical guidance and practical basis for the development of anticancer drugs based on G4 DNA.