疏水无机纳米晶的表面功能化修饰及其生物医学检测应用

Due to their novel optical and magnetic properties, uniform shape and small particle size, the luminescent and magnetic nanocrystals have been drawn great interests in the biomedical applications such as DNA detection, immunoassay, cancer cell fluorescence imaging and magnetic resonance imaging. However, these inorganic nanocrystals are hydrophobic because they are usually synthesized in the oliec acid-oleylamine-1-octadecene mixture solvent, which limits greatly their biomedcial applictions. So, in the current project, the rare-earth-doped NaYF4, LaPO4, and LaVO4 luminescent nanocrystals, magnetic nanocrystals (Fe3O4, Pt-Fe) and quantum dots with novel properties as well as controllable shape and size will be prepared in the oil system. To make these inorganic nanocrystals water-stable, biocompatible, and bioconjugatable, some facile and verstatile surface modification strategies will be developed for the surface functionalization of these hydrophobic nanocrystals by coating with biopolymers. And then the biological labels such as antibodies, peptides and nucleic acids will be conjugated onto the coating shell to obtain the nanobiotags. Finally, these as-prepared nanobiotags will be utilized for the immunoassays, in vivo/in vitro fluorescence imanging and magnetic resonance imagning. In summary, we hope these researches will find potential applications in the ultrasensitive diagnosis of cancers and other serious diseases.

发光与磁性纳米晶在基因检测、免疫分析和癌症诊断（荧光成像和核磁共振成像）等领域倍受关注。发光与磁性优良、尺寸均匀、形貌规则、粒径小的无机纳米晶通常在疏水有机溶剂中制备，颗粒表面疏水，不适合生物医学检测应用。本研究利用溶剂热技术制备系列稀土掺杂发光纳米晶(如NaYF4，LaPO4，LaVO4等)、磁性纳米晶(如Fe3O4，Pt-Fe等)和量子点(如ZnS等)，借助超声乳化、表面聚合及分子置换方法，探索一些简便、通用的修饰技术，在不改变纳米晶的性能、形貌、尺寸和聚集状态的前提下，在疏水纳米晶表面包覆生物相容性大分子，改善纳米晶的水溶性和生物相容性。并在大分子表面进行生物标记物偶联，探索纳米晶在免疫分析、癌细胞与活体荧光成像及核磁共振成像中的应用。以期为癌症等重大疾病的早期诊断提供新材料、新技术、新方法。

在国家自然科学基金“疏水无机纳米晶的表面功能化修饰及其生物医学检测应用（21275015）（2013.01 - 2016.12）”资助下，发展了若干纳米晶表面功能化修饰新方法，构建了若干功能纳米探针，成功用于生化分析检测、细胞成像与活体肿瘤成像研究。共发表SCI论文46篇，其中Anal. Chem.7篇， Angew. Chem.-Int. Edit. , ACS Nano, Nano Lett.， Small各1篇， Nano Res. 5篇，ACS Appl. Mater. Interfaces 3篇。申请发明专利15项。共毕业硕士研究生14人，博士生3人。其中 7人国家奖学金。已超额完成课题研究任务。..1、.发展了高分子包覆的Cu7S4等离子体共振光热纳米探针，利用等离子体共振光热成像技术，成功用于潜在指纹灵敏光热成像与分析检测。（Nano Lett. 2015,；Angew. Chem.-Int. Edit. 2016；Small 2015；Anal. Chem. 2015）.2、.发展了系列荧光、光热纳米探针，成功用于硝基苯类爆炸物TNT的灵敏分析。（Anal. Chem. 2015；2015； TrAC-Trends Anal. Chem. 2015；2015；Chem. Commun. 2013；ACS Appl. Mater. Interfaces 2014）。.3、.发展了若干上转换发光与抗癌药物负载型近红外II区荧光多功能纳米探针，提高了药物靶向性，显著降低生物背景荧光干扰，成功用于抗癌药物活体输运的实时荧光成像示踪。（Nano Res. 2015；2014; TrAC-Trends Anal. Chem. 2015；Trac-Trends Anal. Chem. 2015, 66, 72）。.4、.构建了19F-MRI成像-近红外光热治疗的多功能纳米探针，成功用于活体肿瘤的19F核磁共振成像及近红外光热治疗，实现“诊断+治疗”一体化。（ACS Nano 2016；Nano Res 2015; 2016; ACS Appl. Mater. Interfaces 2016； Anal. Chem. 2016；2016）。