智能响应MRI/NIR荧光双模态纳米探针的构建及其在活体肿瘤成像分析中的应用

Multi-modality imaging with two or more imaging modalities allows integration of the strengths of individual modalities is becoming a trend and frontier of molecular imaging, which has important research significance the field of early diagnosis, therapeutic effect monitoring and the mechanisms research. We design and synthesize core-shell mesoporous silica nanoparticles-MnO2 （MSN@MnO2）nanoprobes with near-infrared fluorescent dye and tumor targeting aptamer. The reduction of MnO2 nanoshell by GSH will release large amounts of Mn2+ ions and quenched NIR fluorescent molecules, resulting in activating the MRI and NIR fluorescent signals and achieving intelligent responsive bimodal MR/NIR fluorescent imaging. Furthermore, based on the high drug loading capability of MSN, nanoprobes can be used for real-time monitoring of drug release. The properties of nanoprobes such as stability, intelligent bimodal MRI/NIR fluorescent imaging ability, chemotherapy and biosafety in a breast tumor xenograft model were systematically investigated. These theranostic nanoprobes combining intelligent responsive dual bimodal MRI/NIR fluorescent imaging and visible drug release are expected to have potential applications in the field of nano-contrast agents and nano-medicine.

多模态成像整合多种成像模式，优势互补，是分子影像发展的新趋势，对肿瘤早期诊断、疗效评价、疾病机理等研究具有重要意义。本项目拟设计合成介孔二氧化硅-二氧化锰核壳结构纳米粒子（MSN@MnO2）、并负载NIR荧光染料，同时表面修饰肿瘤靶向的核酸适体，设计构建具有靶向识别功能的纳米探针。在靶细胞中，MnO2壳层被谷胱甘肽还原解离，释放大量的Mn2+ 离子和被猝灭的NIR荧光染料，产生MRI和NIR荧光双增强信号，实现智能响应的MRI/NIR荧光双模态成像。在双模态成像的基础上，结合MSN高的药物负载能力，将纳米探针进一步应用到成像监控的药物释放。在异种移植乳腺癌的荷瘤小鼠模型中，系统研究所构建纳米探针的稳定性、智能响应双模态成像的效果、药物治疗和生物安全性等。这种集智能响应双模式成像和可视化药物释放于一身的诊疗一体化纳米探针，将在生物纳米造影剂和纳米药物等领域具有潜在的应用前景。

本项目按照项目任务书，开展了MRI/NIR双模态纳米探针的构建及其在活体肿瘤成像分析中的应用。取得的主要研究成果包括：（1）构建几种智能响应多模态探针并研究其在活体肿瘤成像治疗中的应用，实现了肿瘤微环境响应的MRI、NIR成像及肿瘤免疫、光热治疗；（2）构建几种纳米药物/基因递送体系，实现了肿瘤靶向的可控药物递送。本项目共发表SCI论文16篇，包括Chem. Soc. Rev. 1篇、J. Am. Chem. Soc. 2篇、Adv. Funct. Mater. 1篇、Chem. Sci. 1篇、Small 1篇、Anal. Chem. 3篇等。