基于生物成像的体内检测和纳米材料介导的靶向递送药物是智慧医疗研究热点，当前急需突破的技术瓶颈是避免生物自发荧光对体内检测的干扰，以及实现基于特定靶标响应的药物精准释放。本项目拟在前期合成上转换发光纳米复合物（UCNP@MOF）等基础上，利用MOFs外壳高效装载抗肿瘤药物DOX，并在其表面修饰固定核酸链及特异识别靶标（microRNA-21为代表）的封闭核酸链以形成封顶单元，实现靶标响应的DOX精准释放；并巧妙利用UCNPs与DOX形成FRET体系，依据荧光信号的改变，同步实现近红外光下靶标的体内检测，构建基于特定靶标响应的诊疗一体化新型纳米探针。最后，借助乳腺癌细胞和荷瘤小鼠模型，验证其检测microRNA-21及其响应的药物释放效果，探讨其在肿瘤诊疗一体化应用的可行性。本项目整合纳米科学、生物医学等技术构建新型纳米探针，可为临床恶性肿瘤的微无创诊疗及精准医疗提供新的思路和奠定研究基础。

Both in vivo detection based on bioimaging and the targeted delivery of drugs by nanomaterials are research hotspots of intelligent medicine. Currently, how to avoid the interference of autofluorescence on detection in vivo, and achieve precise drug release responding to specific targets are the technical difficult problems that need to be broken through urgently. Based on the preliminary work，especially the synthesis of upconversion luminescence nanocomposites (UCNP@MOF), we propose to construct a novel nucleic acid functionalized UCNP@MOF theranostic nanoprobe responding to a specific target (represented by microRNA-21). The MOFs shell is used to load the antineoplastic drug (DOX) efficiently, then the capping units is formed by a arm-DNA chain and a target-responsive DNA chain, which could release the DOX precisely based on the responding to the target (microRNA as the representative). The fluorescence resonance energy transfer (FRET) system composed by UCNPs and DOX is utilized to detect the target in vivo with the change of fluorescence signal under near-infrared light excitation. Further, by means of the experiments of breast cancer cell lines and tumor-bearing mice models, we will validate the efficiency of detection and drug release responding to microRNA-21 in vivo, and explore the application feasibility in the integration of diagnosis and treatment of cancer. This project integrates multi-disciplinary technologies such as nanoscience and biomedical science to construct an original theranostic nanoprobe, which can provide new ideas and lay a foundation for noninvasive diagnosis and precision medicine of cancer.