新型介孔碳材料为载体的光热刺激响应多功能药物传输体系应用研究

The photothermal therapy using nanomaterials has been recently attracted as an efficient strategy for the next generation of cancer treatments. Mesoporous carbon nanoparticles (MCNs) strongly absorb near-infrared (NIR) radiation and efficiently convert absorbed energy to released heat which can be used for localized hyperthermia applications. Moreover，in contrast to mesoporous silicas, the ordered mesoporous carbon nanoparticles (MCNs) have even higher surface areas and pore volumes, which facilitate larger amount of drug loadings. Therefore, in this project, several photothermal-responsived multifunctional drug delivery systems based on mesoporous carbon nanoparticles as carriers were studied. Compared with chemotherapy or photothermal treatment alone, these combined treatment would demonstrate a synergistic effect, resulting in higher therapeutic efficacy and shorter treatment times.

在本项目中，我们将结合目前纳米药物传输系统的研究热点，在前期研究的工作基础上，利用新型介孔碳纳米颗粒（MCN）的高负载率和近红外吸收独特性能，与现代分析手段相结合，研究建立基于MCN载体为基础的集化疗、热疗、影像、靶向为一体的多功能药物传输体系的可行性。具体内容包括：（1）利用MCN表面富集羧基沉积生物相容性材料羟基磷灰石（CaP）, 构建受pH值响应控释同时又具有近红外热疗功能的MCN-CaP药物运输体系；（2）利用layer-by-layer方法构建可同时运输抗癌药物和基因的MCN-PEI-DNA靶向基因药；（3）利用MCN载体独特的近红外吸收性能构建光热刺激响应多重药物释放体系MCN- - dDNA系统；（4）从细胞层面考察介孔碳颗粒作为载体构建的集化疗、热疗、靶向、影像为一体的多功能药物传输体系的功效，实现化疗结合光热疗、靶向等协同抗肿瘤作用

本课题系统研究了利用新型介孔碳纳米颗粒的高负载率和近红外吸收独特性能，建立基于HMCN 载体为基础的集化疗、热疗、影像、靶向为一体的多功能药物传输体系。利用硅源辅助软模板法，通过优化HMCN颗粒的合成条件，获得具有高比表面积及良好光热吸收转换的HMCN颗粒。以此介孔碳做为载体，DOX为负载药物，采用无机盐快速沉淀及层层自组装技术修饰HMCN，分别建立了针对肿瘤微环境pH及光热刺激响应释放的MCN-DOX-CaP 体系；HMCN-DOX-PEI-Aptamer体系与HMCN-ZIF体系。上述体系的药物负载率为94.6%,对pH具有良好的刺激响应释放性能，经808nm激光照射后，对HeLa肿瘤细胞抑制效果达到82.9%。研究结果表明基于HMCN 载体建立的多功能药物传输体系可有效实现化疗结合热疗、靶向的协同治疗作用。