【作者】 王超；

【导师】 吴水珠；

【作者基本信息】 华南理工大学 ， 材料科学与工程， 2021， 硕士

【摘要】 吲哚半花菁染料由于具有较长的吸收波长和荧光发射波长,常被用于构建可以检测酶类生物标志物的光学探针。本文中,设计并合成了两种基于吲哚半花菁染料的光学探针,并将其用于检测碱性磷酸酶(ALP)和醌氧化还原酶(NQO1)。主要内容如下:(1)设计合成了基于苯并吲哚半花菁的碱性磷酸酶响应型近红外荧光探针X-DPA-Phos。首先对探针的结构进行了表征。之后,考察了荧光探针X-DPA-Phos对碱性磷酸酶的响应性能。由于ALP的酶催化作用,探针分子上的磷酸根基团离去,所生成的荧光生色团X-DPA-OH可在700 nm的激发光下发射出765 nm的荧光信号,由此可实现对ALP的荧光检测,检测下限为8.26 U/L。(2)设计合成了基于吲哚半花菁的醌氧化还原酶响应型光声探针TPA-X-Q。首先对探针的化学结构进行了表征。其次,考察了探针TPA-X-Q对NQO1的光声响应性能。在NQO1的作用下,探针分子上的醌丙酸酯基团离去,从而生成生色团TPA-X-OH,产生强烈的光声信号。其检测下限为0.19μg/m L。并且探针对NQO1的响应表现出良好的选择性、光稳定性及较低的生物毒性。此外,将探针TPA-X-Q用于乳腺癌小鼠模型中,对乳腺癌肿瘤中过量表达的NQO1进行光声检测与成像,利用多光谱光声断层扫描技术(MSOT)的三维光声成像功能,可对肿瘤病灶区域进行定位。更多还原

【Abstract】 Indole hemicyanine is usually employed to design optical probes for detecting enzyme biomarkers,owing to its long absorption and emission wavelength.In this study,two probes based on indole hemicyanine have been designed,and their applications in detection for alkaline phosphatase(ALP)and NAD(P)H:quinone oxidoreductase-1(NQO1)have been explored.The main contents are as follows:(1)The ALP-responsive near-infrared fluorescent probe X-DPA-Phos based on benzoindole hemicyanine has been designed and synthesized.Its chemical structure has been characterized.Then the response capability to ALP of fluorescent probe X-DPA-Phos has been investigated.With the enzymatic reaction by ALP,the phosphate group of X-DPA-Phos is cleaved,and therefore the near-infrared fluorescence signal at 765 nm of the resultant fluorophore X-DPA-OH appears upon 700 nm excitation.Thus,the fluorescence detection of ALP can be achieved and the limit of detection is determined to be 8.26 U/L.(2)The NQO1-responsive optoacoustic(OA)probe TPA-X-Q based on indole hemicyanine has been designed and sythesized.Its chemical structure has been characterized.And the reponse capability to NQO1 of OA probe TPA-X-Q has been investigated.In the presence of NQO1,the quinone propionate group of TPA-X-Q is cleaved,and therefore the probe is transformed into the chromophore TPA-X-OH,consequently evident OA signal is generated.The limit of detection is determined to be 0.19 μg/m L.Furthermore,the probe TPA-X-Q displays several advantages,such as good selectivity,excellent photostability and low biotoxicity.Finally,the probe has been utilized to detect and image the overexpressed NQO1 in the breast cancer-bearing mouse model.Orthogonal-view three-dimensional(3D)images can also be obtained by using multispectral optoacoustic tomography(MSOT),and thus precise localization of the breast cancer tumors can be achieved.更多还原