多功能含钆稀土上转换纳米复合材料的控制合成及其在光控释药和医学影像方面的应用

项目名称： 多功能含钆稀土上转换纳米复合材料的控制合成及其在光控释药和医学影像方面的应用

项目编号： No.51332008

项目类型： 重点项目

立项/批准年度： 2014

项目学科： 一般工业技术

项目作者： 林君

作者单位： 中国科学院长春应用化学研究所

项目金额： 300万元

中文摘要： 多功能无机纳米复合材料在多种模式生物影像、药物传递等方面有广泛的应用前景，为疾病的同时诊断和治疗提供了一种新颖平台，尤其光控药物传输体系的设计与制备近年来备受关注，这是由于光能够提供高度精准的非物理性接触的外部刺激，可达到时间、空间的同时可控。但目前所用的光触发分子通常用紫外光激发，而紫外光毒性比较大，生物组织穿透深度低。在本项目中，我们拟开发一类新的近红外至紫外、含Gd3+的多功能稀土上转换纳米粒子，以此粒子作为纳米传感器和多种模式的影像试剂组装到介孔SiO2中，通过控制反应条件来调节粒子尺寸、介孔SiO2的壳层厚度及孔径大小等；以硝基苯衍生物作为光触发分子，β-环糊精作为孔道口的“开关”共价连接到介孔SiO2的表面，并用PEG和靶向分子叶酸对材料进行修饰以提高其生物相容性和靶向功能，研究材料在体外、体内的靶向传递、光控药物释放以及医学影像中的应用，最终建立一种“诊疗一体化”的药物载体。

中文关键词： 多功能纳米复合材料;近红外-紫光上转换发射;光学成像;核磁共振成像;光控药物传递

英文摘要： Multifunctional inorganic composite nanomaterials have extensive applications in various biomedical fields such as multimodal bioimaging and drug delivery, which provides an unparalleled opportunity and platform for simultaneous diagnostics and therapy of disease. In particular, light can function as a highly orthogonal external stimulus and provides spatial and temporal control in drug delivery, so photo-controlled drug delivery system have attracted much attention in the burgeoning field of nanomedicine. The major hurdle in this process is that phototriggers mostly respond to UV radiation and not to visible or near-infrared (NIR) light. The use of UV irradiation is limited by its toxicity and very low tissue penetration power. In this project, we will open up a kind of novel NIR-to-UV rare earth upconversion nanoparticles containing Gd3+ (labeled as UCNPs) acting as a nanotransducers for photo-controlled drug release as well as upconversion luminescence (UCL) and magnetic resonance imaging (MRI) contrasts. The uniform, monodisperse, core-shell structured nanocarriers (labeled as UCNPs@mSiO2) composed of mesoporous silica coated UCNPs will be designed and fabricated. The size of nanocomposites, the thickness of mesoporous shell and mesoporous size will be tuned carefully by changing various experimental conditions. Then an o-nitrobenzyl ester moiety as a photocleavable linker, and the CD “gatekeeper” that can close the gate of the pore of SiO2 will be conjugated into the surface of mSiO2. And polymer PEG and targeting component folic acid will be used to modify the surface of the materials to increase colloidal stability and water dispersion as well as targeting ability of nanoparticles. Finally, in vitro/in vivo targeting delivery, remote photo-controlled drug release and medical imagings will be investigated in detail so as to obtain a “theranostic” nanocarrier system.

英文关键词： multifunctional nanocomposites;NIR-UV upconversion emission;optical imaging;magnetic resonance imaging;light-controlled drug delivery