双重靶向的多模诊疗探针用于肿瘤MRI/荧光分子成像及光动力/化疗协同治疗研究

Early diagnosis and treatment of cancer is one of the most active areas of research. Design and preparation tumor-targeting theranostic probe, which integrate cancer diagnosis and cancer therapy, has emerged as a new strategy against cancer. Herein, based on the slightly acidic environment of the tumor tissues and the specific surface biomarkers, we design and synthesize a core-shell theranostic probe (C3N4/GQDs@MOF) with targeted molecule and anticancer drug, for the targeting MRI/fluorescence imaging and chemo/photodynamic synergistic therapy. The degradation of iron (III)-based MOF nanoshell in slightly acidic environment will release anticancer drug and the fluorescence of C3N4/GQDs will recover, achieving bimodal MRI/fluorescence imaging. Further, combining C3N4/GQDs as the photosensitizer and the anticancer drug, chemo/photodynamic synergistic therapy will realize. The properties of nanoprobe such as stability, tumor-targeted, bimodal MRI/fluorescent imaging ability, pH responsive drug release, chemo/photodynamic synergistic therapy, and biosafety in a breast tumor xenograft model were systematically investigated. The theranostic nanoprobe combining dual-targeting, multimodal imaging and synergistic therapy are expected to have potential applications in the field of nano-contrast agents and targeting theranostic.

癌症的早期诊断和治疗是当前最活跃的研究领域之一。设计、制备肿瘤靶向性的诊疗一体化探针被视为癌症诊疗的新策略。本项目针对肿瘤微酸环境和癌细胞表面特异性分子标志物，设计一种双重靶向的氮化碳/石墨烯量子点-金属有机框架核壳结构的诊疗探针（C3N4/GQDs@MOF），并负载药物，用以实现肿瘤MRI/荧光成像和光动力/化疗协同治疗。在肿瘤微酸环境中，Fe基MOF壳层发生分解，被猝灭的C3N4/GQDs荧光得到恢复，结合Fe3+，实现MRI/荧光双模成像；同时，C3N4/GQDs在光照下产生单线态氧进行光动力治疗，结合释放出来的药物，实现光动力/化疗协同治疗。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、靶向效应、MRI/荧光成像效果、光动力/化疗协同治疗效果等。这种集多重靶向、多模成像和协同治疗于一体的诊疗探针，将在生物纳米造影剂和靶向诊疗一体化等领域具有潜在的应用前景。

利用纳米材料独特的性质，构建功能化复合纳米体系，对于癌症的精准治疗及能源催化等具有十分重要的意义。本项目以设计和构建功能化纳米体系为目标，完成了几种复合纳米材料的开发及其在生物医学和能源催化应用。具体研究内容包括：（1）构建了一种基于多巴胺和氮化碳（g-C3N4）的荧光探针，用于生物样品中抗氧化物的检测；（2）构建了一种基于DNA和双层羟基氧化钴的荧光探针，实现三磷酸腺苷的灵敏、简单检测；（3）以不同方法处理的碳纳米管和铁酞菁为原料，探究了氧含量对碳基铁酞菁复合纳米材料氧还原性能的影响；（4）采用氧化石墨烯辅助的湿化学反应合成铁酞菁/石墨烯复合纳米材料，通过调控氧化石墨烯的固含量和复合物的还原程度，探究了复合材料的电催化CO2还原反应性能。