基于包覆聚集荧光增强染料的功能氧化硅纳米粒子的生物大分子分析新方法研究

Biomacromolecules are the most important building blocks of living organisms for maintaining biological systems. Some biomacromolecules such as DNA, RNA and protein etc. are closely related to pathogenic genes, genetic diseases, regulation of gene expression, cell proliferation, differentiation and apoptosis, as well as the occurrence and development of cancers. The development of innovative methods for detecting these biomacromolecules is an important task for analytical chemistry. The aim of this project is to design and synthesize novel AIE (Aggregation-Induced Emission) luminogens coated by fluorescent silica nanoparticles, the surface of which will be chemically or biologically modified with functional nucleic acids as recognition molecules. Based on the specific recognition of functional nucleic acids and biomacromolecules, novel fluorescent probes will be constructed through fluorescence enhancement or fluorescence resonance energy transfer produced by the AIE luminogens coated by fluorescent silica nanoparticles. The functionalized fluorescent silica nanoparticles will be employed both as specific recognition moiety for target molecules and as fluorescent signal transducer for constructing analytical microarrays for high throughput analysis of different biomacromolecules and imaging systems for detection of cancer cells.

生物大分子是构成生命体和维持生命现象最重要的物质。某些生物大分子如特定序列DNA、microRNA、蛋白标志物等，与病原基因和遗传疾病、基因表达调控、细胞增殖分化和凋亡以及癌症的发生、发展存在着密切的联系。发展具有创新意义的生物大分子检测技术是分析化学研究的重要方向。本研究旨在设计合成具备优异荧光性质的新型包覆聚集荧光增强染料的氧化硅纳米粒子，将功能核酸通过化学或生物作用修饰于其表面进行功能化。利用功能核酸与生物大分子特异性的识别作用，通过包覆聚集荧光增强染料的氧化硅纳米粒子产生荧光增强或荧光共振能量转移信号，构建荧光探针新体系。并将这些新型包覆聚集荧光增强染料的功能氧化硅纳米粒子作为分析物的特异性识别部位和荧光信号响应部分，构建多种生物大分子高通量分析的微阵列分析器件以及肿瘤细胞的成像检测体系。

氧化硅荧光纳米粒子具有制备方法简单，生物相容性良好，细胞毒性低，表面易于修饰，基质透明不影响激发和发射光透过，包裹于纳米粒子中的染料荧光性质稳定等优势。为克服包裹于硅胶纳米粒子中的染料聚集荧光猝灭，本项目提出了设计合成包覆聚集诱导荧光（AIE）染料、表面以适配体修饰的功能化氧化硅纳米粒子，发展肿瘤细胞的成像检测体系的研究目标。.本项目基于这一思路，设计合成了适配体修饰的、包裹了水杨醛腙或光激活水杨醛腙AIE染料的荧光纳米硅球并成功将其用于肿瘤细胞的荧光成像。这类荧光纳米粒子与包裹了传统染料荧光素的硅球或聚苯乙烯纳米球相比荧光更强，并实现了多波长荧光发射和光激活荧光发射；发展了具有刺激响应特性的荧光分子体系，包括可逆光激活三苯甲醇分子、波长选择性光激活多色水杨醛腙分子、光致变色的罗丹明和结晶紫内酯水杨醛腙-金属配合物、机械力刺激响应的苯甲酮衍生物；构建了AIE小分子探针用于酯酶、半乳糖苷酶、半胱氨酸、巯基离子、焦磷酸根、铝离子的荧光检测体系和细胞成像探针。