针对代谢标志物的分子探针设计与合成

2013 Annual Report of the 973 Project“Design and Synthesis of Biomarkersin the Serum Metabolites”

肿瘤患者的早期准确诊断非常重要,发展简单方便及费用低的诊断新方法具有极其重要的现实意义。大多数疾病的生物标志物都来自血清中的代谢物;但是血清中成分十分复杂,肿瘤代谢物含量低。关键科学问题在于如何,利用高敏感性和特异性的分子探针实现对实现在肿瘤发展初期血清标志物的诊断,由此大大提高肿瘤早期诊断率。该年度在改善荧光探针识别血清标志物的特异性、荧光探针设计新概念、新方法,以及新型荧光传感材料创制三个方面开展了创新研究。取得了一系列具有重要影响力的原创性研究成果。其中针对新型血清肿瘤标志物α-酮戊二酸、肿瘤细胞高尔基体环氧化酶标志物、溶酶体一氧化氮和粘度等特异性探针均为国际首创。对于肿瘤早期诊断以及分子、细胞水平研究肿瘤相关过程提供了重要工具。所提出的荧光探针设计新概念、新方法对于进一步创制高灵敏、高特异性、高稳定性荧光探针奠定基础;构建了基于染料和共聚型高分子、纳米颗粒的新型多功能荧光传感材料,不仅改善染料的荧光性质,而且提高了对肿瘤靶标的特异性识别能力,将进一步促进对肿瘤诊断的准确性,并且可能具备在诊断的同时发挥治疗肿瘤的潜能。

Early accurate diagnosis of Tumors is very important for patients. The development of new simple and low-cost diagnosis methods has extremely important practical significance. Most of the biomarkers of diseases come from in the serum metabolites; but the challenge lies in that serum composition is very complicated and that tumor metabolites content is low in serum. Key scientific problem is how to apply the highly sensitive and specific molecular probes for implementation the recognition of serum markers in the early periods of tumor development, thus greatly improve the tumor diagnosis. This year,our team carries out the innovative study in order to improve fluorescent probes’ specificity to identify the serum markers,to bring about new concepts and new methods to create efficient fluorescent probes and to construct novel multifunctional sensing materials as well as three aspects to. We have made a series of original researches that generate results of important scientific influences. For example, the specific fluorescent probes for alpha ketone glutaric acid as new serum tumor markers, for cell golgi apparatus cyclicoxidase as tumor markers, probes specific to lysosomal nitric oxide and viscosity, are of original creativity. For early diagnosis of tumors, and for researches on tumor-related processes in molecular and cellular level, we provide these new probes as important tools. Our new concepts and new methods to rational design fluorescent probes lay a solid foundation for the further development of high-sensitivity, high-specificity, high-stability fluorescent probes. We have also constructed new type of multifunctional nanoparticles fluorescence sensing materials based on dye and copolymers, which not only improve the fluorescent properties, but also improve the specificity of the tumor targeting and recognition ability,and thus, will further promote the accuracy of tumor diagnosis.