硼酸功能化多光子荧光纳米探针用于肿瘤成像研究

Molecular imaging is of great importance in cancer early diagnosis and exploration of new molecular imaging probes with high sensitivity, high resolution and highly specific targeting ability has been the key point. In this project, near-infrared hydrophobic multiphoton nanophosphors with small size and high luminescence will be prepared and in the meantime, boronic acid moiety containing amphiphilic polymer would be synthesized which could specifically recognize the glycoproteins overexpressed on the cancer cell surface. Then based on the newly proposed facile versatile surface modification strategy, these multiphoton nanophosphors will be converted into biocompatible nanocomposites with high water solubility and specific targeting ability and be further utilized in in vivo targeting and imaging of tumors. Owing to the unique optical properties such as high targeting specificity, long excitation and emission wavelength, low background fluorescence interference and deep penetration of tissues, multiphoton nanoprobes is particularly suitable for specific targeting and in vivo imaging of tumors , therefore, would serve as new candidates and techniques for high sensitive diagnosis of cancers at early stage.

分子影像在癌症早期高灵敏度检测与诊断方面有重要的价值和意义，开发具有高灵敏度、高分辨率、高特异性靶向能力的新型分子影像探针是癌症检测中的关键科学问题。本课题拟合成小尺寸、高亮度近红外发光的多光子纳米晶，设计并合成含硼酸基团（能选择性识别肿瘤细胞表面过渡表达的糖蛋白）的双亲聚合物，发展简单普适的表面修饰技术，实现对无机纳米探针的表面功能化修饰，将多光子发光纳米晶转化为具有良好生物相容性、水溶性、高靶向能力的荧光纳米探针，利用该荧光纳米探针实现对活体肿瘤的灵敏、靶向性成像检测。多光子纳米探针靶向能力高、能长波激发与发射、背景荧光干扰低、组织穿透性强，特别适合活体肿瘤靶向识别与灵敏成像，为癌症的早期超灵敏诊断提供了新材料、新技术、新方法。

发展新型的高灵敏度、高靶向性分子影像探针是实现重大疾病早期诊断的关键。本项目围绕新型发光纳米材料制备、表面功能性质调控以及在生物医学领域的应用研究开展了一系列工作。在本项目的资助下，发展新型的溶剂法设计合成了近红外II区发光的硫化银量子点，借助反应前驱体在不同溶剂体系中饱和度差异，通过优化反应溶剂体系进而控制合成小尺寸、高发光亮度的硫化银量子点。同时发展“一锅法”嫁接不同功能分子(硼酸基团，多肽RGD，烷基疏水链，正电基团)，制备具有良好生物相容性的功能化双亲分子，通过优化包覆方法及改变功能基团以调控发光纳米探针表面性质，实现对纳米探针的尺寸优化，表面亲疏性调控以及功能化。此外，成功制备了高稳定性发光纳米水凝胶(AuNCs@GC)，利用羟乙基壳聚糖的屏蔽作用及局部富集作用，一方面实现全pH范围稳定的纳米水凝胶制备，另一方面，实现了纳米金簇发光性能的显著提升以及对硫化氢的高选择性识别。本项目为新型分子影像探针的开发提供了新材料，也为纳米功能材料表面性质定向调控提出了新研究思路。