聚集诱导发光纳米探针的构筑及在癌细胞靶向诊疗中的应用

To achieve the early diagnosis and therapy of cancer, it's highly desirable to develop cancer cell-targeted imaging and therapy methods. Compared with ultrasound, MRI, and CT imaging techniques, fluorescence imaging has significant advantages in excellent sensitivity, high temporal and spatial resolution. However, conventional fluorescent dyes can easily undergo self-quenching after forming aggregates in biological media. To overcome the aggregation-caused quenching effect, this project will develop new fluorescent materials with aggregation-induced emission (AIE) characteristics, and endow them with advantages of high NIR emission efficiency, strong anti-photobleaching ability, and strong photodynamic activity. Based on their high emission efficiency at aggregation state, AIE compounds can be easily developed into nanoparticles through nano-precipitation methods. The AIE nanoparticles can be further decorated with cancer cell targeting ligands, chemical drugs, and siRNA to form theranostic AIE probes, which can integrate together the fluorescence imaging, photodynamic therapy, chemical therapy and gene silencing therapy. The implementation of this project will significantly promote the early diagnosis and therapy of cancer.

为了实现癌症的早期诊断和治疗，需要发展针对癌细胞的特异性成像和治疗方法。相对于超声、核磁共振、计算机断层扫描等成像方法，荧光成像具有高灵敏性、高时空分辨率等突出优点。然而传统的有机荧光染料在生物介质中易发生聚集，从而导致荧光的自我猝灭。为了克服这一聚集诱导猝灭缺陷，本项目将设计合成新型聚集诱导发光材料，并赋予其近红外发光效率高、抗光漂白能力强、光动力学活性好等优点。由于其在聚集态的高发光效率，可通过纳米沉淀法直接制备高效发光的纳米粒子，进一步通过在聚集诱导发光纳米粒子上修饰癌细胞的识别配体、化学药物和短干扰核糖核酸等，可将荧光成像、光动力学治疗、化学药物治疗和基因沉默治疗等融合到一起，建立诊疗一体的聚集诱导发光纳米探针，实现癌细胞靶向的特异性荧光成像和治疗。通过本项目的实施，将为癌症的早期诊断和治疗起到重要的推动作用。

癌症的早期诊断和治疗迫切需要针对癌细胞特异性成像和治疗的方法。荧光成像具有高灵敏性、高时空分辨率等优点，但传统有机荧光染料存在聚集猝灭发光缺陷。为了克服这一缺陷，本项目开展了新型聚集诱导发光探针（AIE）的研发及在癌细胞靶向高时空分辨诊疗中的应用研究，取得了以下创新性成果：（1）发展了光激活AIE成像探针，实现了癌细胞内脂滴、溶酶体等细胞器的特异性高时空分辨荧光成像；（2）协同分子内运动受限、激发态分子内质子转移、光诱导电子转移等荧光传感机制，实现了对肿瘤相关的钙离子等的高灵敏和特异性检测；（3）利用AIE分子的聚集发光效应和聚集毒理效应，通过协同破坏癌细胞内的线粒体和溶酶体，实现了针对癌细胞的靶向诊疗一体化。通过本项目的实施，将荧光成像、光动力学治疗、化学药物治疗等融合到一起，建立了诊疗一体的AIE纳米探针，实现癌细胞靶向的特异性荧光成像和治疗，为AIE探针在癌症的早期诊断和治疗中的应用起到了重要的推动作用。以第一或通讯作者在Adv. Funct. Mater., Chem. Sci.等期刊发表SCI论文14篇，ESI高被引论文2篇，封面论文1篇，申请中国发明专利6项，获授权中国发明专利2项。