靶向性近红外二区扩环细菌卟吩分子探针的构建及应用

With low photo-damage, deep imaging depth and high spatial resolution for bio-tissue, NIR-II molecular probe can label epidermis cancers efficiently and be applied in fluorescent imaging significantly. The overall objective of this project is to obtain four types of molecular probe based on fused-bacteriochlorin through chemical syntheses and apply in cells, in vitro and vivo optical imaging. The key research is to synthesis NIR-II molecular probes based on fused-bacteriochlorin by introducing anti-EGFR Affibody and tuning different π-conjugation to adjust fluorescent emission wavelength. Molecular probes based on fused-bacteriochlorin with targeting ability and NIR-II were obtained. Then, the optical imaging measurement of molecular probes such as specificity, binding property, in vivo pharmacokinetics, and tumor-to-normal tissue ratio (T/N ratio) was carried out. The aim of this project is to construct molecular probes with various fluorescent emission wavelength for screening the best performance probe, establish research system of molecular probes for molecular imaging of epidermis cancers and elucidate their relationship and influencing factors. Early diagnosis of epidermis cancers can be realized which has a significant scientific value to increase cure rate of cancers and prolong survival time of patients through the successful implementation of this project.

近红外二区分子探针(1000nm～1700 nm)具有对生物组织光损伤小、透射深度深、空间分辨率高的特点，可对表皮癌组织进行有效标记，在荧光成像中具有显著的应用优势。本项目以化学合成法构建四类扩环细菌卟吩分子探针，并应用于细胞、离体和活体荷瘤小鼠荧光成像中。重点研究靶向性近红外二区扩环细菌卟吩分子探针的构建，通过引入对表皮生长因子(EGFR)特异性结合的亲和小体和不同大小π-共轭体系，得到具有靶向性近红外二区扩环细菌卟吩分子探针。同时，对探针的特异性、亲和力、药物动力学和肿瘤与正常组织荧光对比值(T/N值)进行测试。实现不同荧光发射波长分子探针的成功制备，建立分子探针对人表皮癌组织分子影像学的研究体系，阐明两者之间的关系和影响因素。通过本项目的成功实施，可实现对表皮癌组织的早期诊断，对提高癌症的治愈率、延长病人的生存期，具有重要科学研究价值。

近红外荧光染料在荧光成像技术中具有重要的应用前景，其对生物组织的光损伤小，所达到的透射深度深、空间分辨率高，可对表皮癌症组织进行有效标记。本项目利用卟啉及其前体进行衍生，发展了两类近红外卟啉荧光染料；高效合成了一系列近红外N-混杂卟啉荧光染料；发展了一系列七元单缩合氟硼产物BOPYIN和双缩合氟硼产物Diazaborepin，合成过程简单高效，是对六元BODIPY母核扩环的一类有机氟硼产物，在发光性能和绝对构型等方面具有自身独特优势；单缩合氟硼产物配体由于周环大位阻基团和分子内氢键的存在，不仅具有ESIPT效应，还具有AIE效应，显示其在有机发光材料领域中的潜在应用；双缩合氟硼产物的配体存在稳定的分子内氢键（七元N-H‥N），研究表明该类配体具有明显的ESIPT效应，且其质子转移速度随取代基不同而变化。通过本项目的实施，首次设计合成了近红外卟啉和七元氟硼荧光染料，深入揭示了七元氟硼染料的光物理性能、绝对构型等变化规律及其作为生物成像试剂方面的可行性，制备得到的高荧光量子产率染料，既丰富了卟啉及其前体七元有机氟硼荧光染料的合成技术，又为其生物和材料领域中的应用提供了理论参考。