針對代謝標志物的分子探針設計與合成

段春迎++肖義++樊江莉++朱為宏

摘 要：腫瘤患者的早期準確診斷非常重要，發展簡單方便及費用低的診斷新方法具有極其重要的現實意義。大多數疾病的生物標志物都來自血清中的代謝物；但是血清中成分十分復雜，腫瘤代謝物含量低。關鍵科學問題在于如何，利用高敏感性和特異性的分子探針實現對實現在腫瘤發展初期血清標志物的診斷，由此大大提高腫瘤早期診斷率。該年度在改善熒光探針識別血清標志物的特異性、熒光探針設計新概念、新方法，以及新型熒光傳感材料創制三個方面開展了創新研究。取得了一系列具有重要影響力的原創性研究成果。其中針對新型血清腫瘤標志物α-酮戊二酸、腫瘤細胞高爾基體環氧化酶標志物、溶酶體一氧化氮和粘度等特異性探針均為國際首創。對于腫瘤早期診斷以及分子、細胞水平研究腫瘤相關過程提供了重要工具。所提出的熒光探針設計新概念、新方法對于進一步創制高靈敏、高特異性、高穩定性熒光探針奠定基礎；構建了基于染料和共聚型高分子、納米顆粒的新型多功能熒光傳感材料，不僅改善染料的熒光性質，而且提高了對腫瘤靶標的特異性識別能力，將進一步促進對腫瘤診斷的準確性，并且可能具備在診斷的同時發揮治療腫瘤的潛能。

關鍵詞：熒光分子探針 血清 腫瘤標志物 診斷

Abstract：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.

Key Words：Fluorescent molecular probe；Serum；Tumor marker；Diagnosis

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