基于糖树状结构的光控超分子复合载药体系的构建与靶向诊疗研究

Nowadays, cancer is one of the major diseases to threaten the human life and healthy seriously in the world. Early diagnose and timely therapy is the key point to prevent and cure the cancer. Unique transmembrane glycoprotein receptors that recognize specific sugar ligands are abnormally expressed on the surface of cancer cells, and sensitive detection of this type of receptor can lead to early diagnosis and treatment of cancer. However, the reported fluorescent glycoprobes mainly based on the specific recognition of monosaccharide and ASGPR with problems such as low affinity and a certain degree of false positive. In order to improve the affinity between sugar and receptors, thus to improve the reliability of the results, a kind of host-guest supermolecule amphiphilic complex using glycodendrimer as the targeting group, porphyrin as photosensitizer and fluorescence report group is constructed and applied to load Anti-cancer drugs. Moreover the as-constructed theranostic system are further applied to tumor diagnosis and treatment in vivo, offering a more reliable method and technology for early accurate diagnosis and high-efficiency precise therapy of cancer.

癌症是全球范围内威胁人类生命健康的重大疾病之一。早期诊断和治疗是预防、治愈癌症的关键。研究表明，癌细胞表面异常表达的糖蛋白受体可特异性识别糖配体，对于这类跨膜糖蛋白受体的灵敏捕捉可实现癌症的早期诊断治疗。已报道的糖靶向荧光探针主要依赖单糖分子与ASGPR的特异性识别，亲和力较低，存在一定程度的假阳性。本项目致力于提高糖与受体间的亲和力，从而提高结果的可靠性，设计构建一种基于半乳糖树为靶向基团，卟啉为光敏剂以及荧光报告团的主客体超分子两亲性络合物，并利用其负载抗癌药物，通过光控定点释放光敏剂与抗癌药物，分别应用于肿瘤的光动力治疗与药物治疗，为实现癌症早期精确诊断和高效精确治疗提供新方法和新技术。

本项目设计合成了一系列对生物活性小分子（Cys、H2S、HOBr）有特异识别性能的新型荧光探针（磺酰胺结构、萘酰亚胺结构探针等），并对其分析性能进行分析，建立了若干测定半胱氨酸、硫化氢、HOBr等目标物的新技术和新方法，探针选择性和灵敏度高。同时，利用癌细胞内内源性活性小分子的靶点作用，实现了癌细胞的靶向标记。根据前面所合成的荧光探针的性能试验结果，对探针的结构与功能之间的关系进行探讨。本项目的开展为新型荧光探针的开发提供新的研究思路，为生物活性小分子提供简便经济、高灵敏度和高选择性的快速检测新技术和新方法，也为癌细胞内特定活性小分子的靶向检测提供了思路。