顺磁性金属离子掺杂的双功能CuInS2纳米晶的合成及性质研究

Doping with paramagnetic metal ions such as Gd3+ or Mn2+ makes semiconductor nanocrystals luminescent and magnetic, suitable for bifunctional bioprobes acting as luminescent labels of photoluminescence imaging (PI) and contrast agents of magnetic resonance imaging (MRI) at the same time. However, such bioprobes which have been prepared up to now are either toxic or unstable, and can't meet the requirements of practical applications. To overcome these problems, we suggest the use of water-soluble paramagnetic metal ions doped CuInS2 nanocrystals prepared by thermal decomposition of single-source precursor and subsequent phase transfer assisted by phospholipid micelles. CuInS2 nanocrystals are low-toxic and stable. Moreover, the wavelength of their emission can be tuned to near infrared, which is advantageous for in-depth detection. Doping semiconductor nanocrystals is still a big challenge. The method of thermolysis of single-source precursor is effective to dope semiconductor nanocrystals with paramagnetic metal ions while their fluorescence is retained. To optimize the function of nanocrystals and lay a foundation for their application, the effects of different conditions of synthesis and phase transfer on the properties of the doped CuInS2 nanocrystals including photoluminescence and enhancement of MRI signals will be studied in this project.

Gd3+，Mn2+等顺磁金属离子的掺杂使得半导体纳米晶同时具有荧光和磁性，可以作为同时应用于荧光成像和核磁共振成像造影的双功能生物探针。但是已经制备出来的掺杂型双功能生物探针往往有毒或者不稳定，不符合实际应用的要求。为此，本项目提出单源前驱体热分解以及后续磷脂包覆相转移的方法制备水溶性顺磁金属离子掺杂的CuInS2纳米晶用作双功能生物探针，这种纳米晶性能稳定且低毒，而且荧光可调至近红外波段，更加有利于深度检测。目前半导体纳米晶的掺杂仍然非常困难，单源前驱体热分解法有利于在保留纳米晶荧光性质的前提下，将顺磁性金属离子掺入CuInS2纳米晶中，实现其双功能。项目主要通过研究不同的合成条件和相转移条件对顺磁性金属离子掺杂的CuInS2纳米晶的荧光和核磁共振成像造影性质的影响，优化这种双功能纳米晶，为其应用奠定基础。

将荧光成像和核磁共振成像结合起来有望能够在生物成像中同时达到高空间分辨率和深组织穿透性，而开发高性能低毒的光磁双功能生物探针是实现这一想法的关键。在本项目中，我们主要研究了顺磁性金属离子Gd3+，Mn2+掺杂的CuInS2纳米晶的合成及其在生物体内外的荧光和核磁共振造影性质。首先，通过高温热分解金属硫醇络合物和双亲聚合物包裹的方法，合成了水溶性的CuInS2:Gd3+纳米晶，发现虽然Gd3+的掺杂会略微降低纳米晶的荧光效率，但CuInS2:Gd3+纳米晶仍具有~1%的荧光效率，并且Gd3+的掺杂使得纳米晶具有12.84 mM-1 s-1的纵向弛豫率(r1)，能够显著增强T1加权像。其次，以谷胱甘肽和柠檬酸根为络合剂，在水相中直接合成了水溶性CuInS2:Mn2+纳米晶，并发现继续包裹ZnS层能够显著提高纳米晶的稳定性和荧光效率，得到的CuInS2:Mn2+/ZnS纳米晶具有~12%的荧光效率，纵向弛豫率(r1)达到了40.59mM-1 s-1。最后，我们评估了CuInS2:Mn2+/ZnS纳米晶用于生物成像的可行性，发现CuInS2:Mn2+/ZnS纳米晶具有很低的细胞毒性，进入细胞后仍具有良好的荧光性质，并在老鼠体内表现出了优异的核磁共振成像造影效果。这些研究证明顺磁性金属掺杂的CuInS2纳米晶能够作为光磁双功能生物探针用于荧光-核磁共振双模成像。