间充质干细胞输送载药半导体聚合物量子点靶向治疗肿瘤的研究

Cancer is a global medical problem and seriously imperils the people’s health and life. Therefore, it is critical to develop new anticancer medicine with good treatment effect and less side effects. In recent decades, a great effort has been done to develop new anticancer medicine, but most of them cannot effective target the cancer and do not have very good treatment effect. In this project, we designed the anticancer system with aptamers and mesenchymal stem cells as the dual-targeting elements and chose the semiconducting polymer dots as the carrier. We can precisely and real-time monitor the distribution and release of the loading medicine in the polymer dots by the fluorescence imaging system. The research mainly includes the synthesis of the polymer functionalized by the anti-cancer medicine and the preparation of polymer dots by nano-reprecipitation method. Effectively dual-targeting is realized by the aptamers and mesenchymal stem cells. The property and efficacy of the anti-cancer system are evaluated by in vivo and in vitro experiments and realize the effective treatment finally.

癌症严重威胁着人类健康，已成为全球性的医疗难题，因此设计治疗效果好、毒副作用小的抗癌药物输送体系具有十分重要的意义。然而目前大部分的抗癌药物因靶向效率低大大降低了对肿瘤的治疗效果。本项目设计了以核酸适配体和间充质干细胞为双重靶向的抗癌药物体系，并采用半导体聚合物量子点做药物载体，借助荧光成像系统实时检测药物体系在生物体内的循环及药物分子的释放。该研究主要包括合成侧链连接抗癌药物分子的功能聚合物，利用纳米再沉淀法制备载药半导体聚合物量子点，并利用核酸适配体和间充质干细胞实现双重靶向载药纳米颗粒，通过体外细胞实验和体内动物实验评价该药物输送体系的抗癌性能。最终实现载药体系的靶向输送并高效治疗肿瘤疾病。

通过RNA干扰（RNAi）介导靶基因沉默的小干扰RNA（siRNA）在探索基因功能以及治疗多种疾病方面收到了越来越多的关注。但是，由于siRNA在体内输送的过程中易被降解且自身带负电荷无法有效地进入细胞等因素限制了基于siRNA治疗方法的发展。本项目中，描述了基于半导体聚合物点（Pdots）的纳米平台的构建方法，以实现有效的siRNA递送。采用纳米共沉淀法将阳离子脂质体G0C14引入Pdots，构建siRNA的纳米载体。含G0C14的聚合物点（G-Pdot）不仅保留了出色的荧光特性，而且增强了细胞摄取siRNA的能力。在聚合物点（G-Pdot）中带正电的G0C14通过静电吸引作用负载带负电的siRNA，而G-Pdot/siRNA复合物仍保持带负电荷，避免了对细胞生长环境的扰动。与商业试剂Lipofectamine相比，此纳米平台基因沉默效率相当，且细胞毒性低。此外，纳米药物在体内显示出良好的肿瘤抑制作用，表明基于Pdots的siRNA药物载体可用于靶向基因递送并实现有效的基因干扰治疗。研究结果表明，此类纳米平台是一种有前途的荧光成像指导siRNA递送平台。