荧光成像及手性特异性生物识别

Fluorescence Imaging and Chiral Specific Biological Recognition

癌症是威胁人类健康的重大疾病之一,实现早查早治是降低癌症死亡率的重要手段。目前在癌症的众多识别方式中,荧光检测凭借无创伤、检测快和可视化等优点受到了持续关注。文章对荧光探针靶向识别肿瘤的研究新进展进行了综述;对赋予荧光探针靶向性的叶酸(FA)和叶酸受体(FR)介导研究进展进行了介绍和深入分析。叶酸受体是癌细胞表面过量表达的特有物质,利用叶酸和叶酸受体特异性结合的特点,叶酸对荧光探针分子进行修饰可赋予荧光探针识别癌细胞的靶向性。叶酸受体有4种亚型(FRα,FRβ,FRγ和FRδ),前两者FRα和FRβ因分别在癌细胞和炎症巨噬细胞表面过量表达而备受关注,FRα和FRβ约有70%的同源性,两者均具有能与叶酸结合的特性,造成了荧光探针分子在生物识别过程中难以区分癌细胞和炎症巨噬细胞的弱势;针对叶酸修饰荧光探针难以区分叶酸受体亚型造成癌细胞和炎症巨噬细胞混淆问题的结构性缺陷,分析了两种叶酸受体亚型结构具有的手性区别特征:FRα和FRβ主要区别位于三个末端未翻译区,有三种不同手性特征的氨基酸形成一个用来包结叶酸分子的三角空腔,分别固定在氨基酸堆积体节点上的三种氨基酸形成了不同手性特性的区域性“手性空间”。FRα和FRβ本身的结构对不同的配体表现出立体差异性。讨论了基于叶酸受体亚型存在的“手性空间”差异性,构建叶酸受体亚型荧光及手性识别探针的可能性;有望借助光谱成像,通过手性荧光探针分子对氨基酸的识别区分叶酸受体两种亚型,实现可视化区分肿瘤细胞和炎症巨噬细胞的识别难题,进而提高癌细胞识别的准确性;文章介绍了手性荧光探针识别氨基酸原理及结构优化设计进展;近年来手性量子点对氨基酸不同对映体的研究备受关注。对无机手性量子点手性产生的本质特征和氨基酸对映体的识别特性进行了总结分析。最后对荧光探针及手性识别领域进行了展望。

Cancer is one of the major diseases threatening human health.Early detection and early treatment are important means to reduce cancer mortality.At present,in many ways of cancer recognition,fluorescence detection has attracted more and more attention due to its advantages of non-invasive,fast detection and visualization.In this paper,we reviewed the new progress of fluorescent probe targeted tumour recognition and introduced and analyzed the research progress of folate(FA)and folate receptor(FR)mediated fluorescence probe targeting.Folate receptor(FR)is a specific substance over expressed on the surface of cancer cells.Using the characteristic of specific binding between folate(FA)and folate receptor,folic acid can modify the fluorescent probe molecules to give the fluorescent probe the ability to recognize cancer cells.There are four subtypes of folate receptor(FRα,FRβ,FRγand FRδ).The former two FRαand FRβare highly expressed on the surface of cancer cells and inflammatory macrophages,respectively.FRαand FRβhave about 70%homology.Both of them can bind to folate,which makes it difficult for fluorescent probes to distinguish cancer cells from inflammatory macrophages in the process of biological recognition.It is difficult to distinguish folate receptor subtypes by modified fluorescent probes,which leads to confusion between cancer cells and inflammatory macrophages.The chiral characteristics of the two folate receptor subtypes are analyzed:FRαand FRβis mainly located in three untranslated regions.Three kinds of amino acids with different chiral characteristics form a triangular cavity to bind folate molecules.The three kinds of amino acids fixed on the nodes of amino acid accumulation form a regional“chiral space”with different chiral characteristics.The structures of FRαand FRβare different for different ligands.Based on the“chiral space”differences of folate receptor subtypes,the possibility of constructing fluorescent and chiral recognition probes is discussed.It is expected that with the help of spectral imaging,the two folate receptor subtypes can be distinguished by the recognition of amino acids by chiral fluorescent probes,and the recognition problem of tumor cells and inflammatory macrophages can be realized to improve the recognition ability of cancer cells in this paper,the principle of amino acid recognition by chiral fluorescent probes and the progress of structural optimization design are introduced.In recent years,the research of chiral quantum dots on different enantiomers of amino acids has attracted much attention.This paper summarises the nature of chiral generation of inorganic chiral quantum dots and the recognition of amino acid enantiomers.Finally,the prospect of fluorescent probes and chiral recognition is discussed.