近红外光/磁双模态肿瘤靶向显影剂的研究

Tumor is one of diseases serious threating human life and health. It has been demonstrated that early diagnosis is crucial to prolong the survival time for cancer patients. Early diagnosis and treatment are one of the most effective methods for prevention and treatment of cancer. Hence, the development of targeted tumor-imaging techniques with sufficient specificity and sensitivity is necessary for cancer diagnosis. Based on this, we propose a new strategy by optical and magnetic resonance dual-modal intelligent imaging for early diagnosis of tumor. According to the acid feature of tumor, a series of pH-activated NIR cyanine probes were designed and synthesized as the core structure of tumor specific imaging agent. Modification of probe with a targeting molecule ( folic acid, polypeptide and hydrophobic cations) improves the tumor-targeted and specificity, further modification of the probe with glucosamine will be carried out for enhancing its biocompatibility and aqueous solubility in order to obtain tumor-targeted and specificity contrast agent. On this basis, the structure-activity relationship of probe will be further studied to optimize the performance of the contrast agents. And then conjugation of probe with MRI contrast agents ligands (DTPA, DOTA or DO3A), functionalization with gadolinium ions to construct tumor-targeted fluorescent and magnetic resonance dual-modal contrast agent. The contrast agent is expected to provide more reliable and comprehensive approach to cancer treatment.

癌症严重威胁着人类的健康与生命，而癌症的早期诊断是提高癌症患者治愈率的关键，早查、早诊、早治已成为癌症预防及治疗中最行之有效的方法。因此，研发特异性高灵敏度的检测技术，用于肿瘤早期诊断是十分必要的。基于此，我们提出基于光/磁双模态智能成像的肿瘤早期诊断技术的研究课题。利用肿瘤细胞的弱酸性特征，设计合成pH激活型近红外菁类荧光探针作为肿瘤特异性成像剂的母体；通过肿瘤靶向物质（叶酸、多肽和亲脂性季铵离子）的修饰提高显影剂的靶向性和特异选择性；通过氨基葡萄糖的改性改善其水溶性和生物相容性，提高探针的肿瘤光学成像性能，从而获得兼具肿瘤靶向性和特异性的多功能显影剂。在此基础上，对探针的构效关系进行进一步研究，完善所得显影剂的性能，并化学键合磁共振造影剂配体DTPA、DOTA或DO3A，再功能化钆离子，构筑肿瘤靶向光/磁双模态智能显影剂。由此所构筑的智能显影剂有望为肿瘤诊治提供更可靠和全面的方法。

癌症严重威胁着人类的健康与生命，而癌症的早期诊断是提高癌症患者治愈率的关键。早查、早诊、早治已成为癌症预防及治疗中最行之有效的方法。因此，研发高特异性高灵敏度的检测技术，用于肿瘤早期诊断是十分必要的。基于此，我们旨在研发能高特异性对肿瘤细胞进行精确显影的荧光探针。基于肿瘤细胞的弱酸性特征，我们首先设计合成了一系列pH激活型近红外花菁类荧光探针，然后在分子中引入糖基及亲脂性阳离子以提高探针的肿瘤靶向性、水溶性及生物相容性，得到了兼具肿瘤靶向性和特异性的显影剂，成功用于癌细胞的特异性成像。而后我们进一步将探针与纳米金通过特异性肽序列相连，进一步提高探针对肿瘤细胞的特异选择性的同时，还实现了荧光介导的对肿瘤的精确光热治疗，在肿瘤的诊疗一体化领域具有良好的应用前景。在此基础上，我们还尝试构建了光/磁双模态探针，并对相关磁性纳米材料及AIE材料的合成及性能进行了研究，以拓展多模态显影剂的构建方法及应用领域。