新型二硫化钼糖荧光复合材料的自组装及其癌细胞标记的基础研究

The structurally and functionally diverse sugar receptors on the cell surface are important signaling molecules, which modulate a number of physiological and pathological events. Recent investigations suggest that these receptors can participate in oncological processes such as cancer development, metastasis and apoptosis. As a result, sensitive probing of these sugar-receptor interactions may not only boost the development of cancer research, but also provide effective tools for targeted cancer theranostics. Thin-layer molybdenum disulfide (MoS2) is rapidly emerging as a surrogate material of graphene due to its low cost, better structural homogeneity as well as facileness in large-scale preparation. MoS2 thin flakes also have good water solubility and high biocompatibility, making them suited for development of biosensors. On the basis of our previous research as regards the construction of fluorogenic composite materials for biosensing, this program exploits the simple and accurate “self-assembly” technique to fabricate fluorogenic composites between glycosyl dyes and MoS2 thin layers. By the fluorescence resonance energy transfer between the glycodyes and the material, the fluorescence of the former can be quenched. The selective binding between the glycodyes and their receptors may cause dissociation of the composite material, recovering the fluorescence. The materials will be further used to stain cancer cells and slices of mice tumor xenografts and of clinical cancer patients to demonstrate their practicality. Meanwhile, the sensing performance of the MoS2 thin layer-based composites will be compared thoroughly with those based on graphene. This project aims at developing a new class of composite materials for the rapid and economic diagnosis of cancer.

癌细胞膜上含有特殊可识别糖的受体蛋白，可参与癌症的发展及转移等过程。于是对于这些癌细胞表面特殊糖受体蛋白的选择性、高灵敏标记不但有利于推动肿瘤学科发展，还可为癌症的靶向诊疗提供有效工具。二硫化钼是近年来新兴的石墨烯替代材料，其成本低廉，易于标准化与大规模制备，且自身具备较高的水溶性和生物相容度。基于对荧光复合传感材料构建的前期基础，本项目应用精确的分子自组装技术，将多种含不同糖基的荧光染料与二硫化钼薄层有序结合，经荧光共振能量转移机制获得荧光淬灭的复合材料，通过与糖受体蛋白的特异性识别解离复合体系使荧光重塑。进一步应用此类材料对不同种类癌细胞和正常细胞进行选择性标记与区分，最终应用接瘤老鼠及临床肿瘤患者组织切片验证其实用价值。还将系统性比较此类硫化钼材料相比石墨烯在标记性能方面的优势，期待发展新型可用于癌细胞及肿瘤组织特异性荧光标记的经济快捷诊断工具。

恶性肿瘤细胞膜上含有可与糖发生选择性识别作用的受体蛋白，糖与其受体蛋白的细胞间识别介导了多种人类重大疾病的发生与发展。本项目通过构建基于糖基荧光探针的复合材料，借助糖基化合物对受体蛋白的荧光标记性能及材料基底的光动力学治疗性能，为癌症的诊疗提供了新的化学工具。本项目研究中，基于二维硫化钼材料具有良好的光学性能和生物相容性，将多种含不同糖基的荧光探针与二硫化钼通过水溶液自组装构建形成糖基复合材料，利用材料表面糖基团对细胞表面糖类受体蛋白的靶向亲和能力及材料基底的光动力学性能，实现了肝癌与乳腺癌细胞的荧光标记和光动力学治疗一体化。此外，应用该复合材料体系，还实现了肝癌组织切片的选择性荧光标记。通过本项目的研究，发展了新型可用于癌细胞诊疗及肿瘤组织特异性荧光标记的新化学工具。

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