具有pH响应的光磁功能化介孔氧化硅载体的制备及其在药物控释和医学影像方面的应用

Most solid tumors have lower extracellular pH compared to the surrounding healthy tissue, and the pH drop experienced during endocytosis is a common phenomenon. So, pH-triggered mesoporous silica based nanocarriers have attracted much attention in the burgeoning field of nanomedicine. In this project, we will construct a multifunctional drug carrier system with luminescence, magnetic resonance image and pH stimuli-responsive properties. First we will synthesis mesoporous silica particles with size of 50-100 nm, followed by functionalization with Gd3+ based upconversion nanoparticles with uniform size and good dispersity. The particle size, the pore size and structure, the luminescence property and the magnetic resonance imaging of the nanocomposites will be tuned carefully by changing various experimental conditions. Polyelectrolyte multilayers (PEM) composed of poly(allylamine hydrochloride) (PAH) and poly(styrene sulfonate) (PSS) hydrogel, degradable polymer PDPAC12 will be coated onto the nanocomposite surface via layer-by-layer (LbL) technique。The system can accomplish first target specific cells/tissues with “zero release” and then execute locally release mediated by pH stimuli. The in vitro/in vivo targeting delivery, pH-dependent controlled release, medical imagings will be investigated in detail. This study will provide some scientific and practical data for the diagnosis and treatment of cancers.

由于肿瘤组织的pH比正常组织低，且细胞吞噬过程中的pH变化是普遍现象，具有pH响应释放行为的多功能介孔SiO2药物传输体系的设计与制备近年来备受关注。在本项目中，我们拟构建一种集荧光、磁共振成像和pH刺激响应释放性能于一体的多功能智能纳米药物载体。首先控制合成尺寸均一、分散性良好、粒径50-100 nm的介孔SiO2纳米粒子，然后将其表面用含Gd3+上转换发光材料修饰，通过控制反应条件来调节复合材料的尺寸、孔径和结构，优化材料的上转换发光成像和核磁成像效果。采用层层自组装法将pH敏感的溶涨型的聚电解质层PAH/PSS，和降解型的PDPAC12包覆到光磁功能化的介孔SiO2外表面形成有机聚合物壳层，实现药物分子在达到靶点前“零释放”，到达肿瘤组织后pH变化下的响应性释放。研究复合材料在体外/体内的靶向传递、pH刺激响应释放以及医学影像中的应用，为肿瘤等疾病的诊断和治疗提供科学实验基础。

在本研究中，我们拟构建一种集荧光、磁共振成像和pH刺激响应释放性能于一体的多功能智能纳米药物载体。获得的主要研究结果如下：（1）合成尺寸均一、分散性良好的介孔氧化硅纳米粒子，表面修饰Gd2O3:Yb3+,Er3+上转换纳米发光材料。采用层层自组装将聚烯丙基胺盐酸盐/聚苯乙烯磺酸钠(PAH/PSS)聚电解质层（PEM）包覆在光功能化的介孔氧化硅外表面获得具有pH响应、上转换荧光成像、磁共振成像功能的多功能药物载体体系。（2）制备粒径均一的Gd2O3:Yb3+,Er3+@nSiO2@mSiO2，在其表面修饰生物降解的壳聚糖高分子材料，得到pH响应释放的多功能纳米药物载体。（3）制备具有上转换荧光、磁共振成像和磁靶向的多功能空心纳米药物载体。