MicroRNA响应的19F MRI/近红外分子探针对肺癌的靶向诊断和治疗

肺癌是威胁人类健康的重要疾病，其发病率和死亡率逐年上升，因此，发展多模态分子影像技术以获取多方位，高分辨信息，明确肺癌的分子机制并为其早期诊疗提供帮助，具有重要的理论意义和实用价值。本项目主要内容是设计合成MicroRNA响应的19F MRI/近红外分子探针，实现对肺癌的靶向诊断和治疗。拟利用19F SiQDs 作为双模态（磁共振和近红外）检测基元，在此基础上修饰上能对肺癌细胞A549有特异性响应的杂化DNA的壳层，形成DNA-19F SiQDs壳核结构的纳米复合体。通过DNA壳层中适配体介导的识别作用，实现该分子探针对肺癌细胞A549的高效识别；通过肺癌中过表达的miR-21的互补配对作用，触发DNA-19F SiQDs的19F MRI信号从无到有，同时也能增强19F SiQDs的荧光信号，并进一步导致肺癌细胞的程序性凋亡，实现从细胞到活体层面的肺部肿瘤的靶向诊疗。

Nano-constructs that can achieve multimodality imaging and drug delivery combine the strengths of each modality together with therapy. A traceable and aptamer-targeted nano-construct has now been developed, the multifunctional nano-construct was obtained by a 19F silica quantum dots core with a programmable DNA hybrid shell, and the multimodality imaging was triggerd by microRNA. Once the nano-constructs had been delivered into lung cancer cells A549 by aptamer mediated recognition and endocytosis, the overexpressed endogenous miR-21 served as an exclusive key to disorganize the shell of the nano-constructs by competitive hybridization with the DNA hybrid, which led to a enhancement of the 19F MRI and fluorescence signal. More importantly, it also can led to a sustained lethality of the lung cancer cells. The results demonstrate great potential of such multifunctional nano-constructs for real-time dual-modality imaging during targeted gene therapy.