电磁场系统驱动纳米机器人在荧光/T1-T2 MRI引导下的肿瘤光热与化疗研究

Attributed to the obstacles of multiple biological barriers in the human body, conventional chemotherapeutic drugs cannot be delivered directly to the tumor site. Although multifunctional drug nanocarriers have achieved considerable progress in diagnosis and treatment for malignant tumor, its targeting efficiency to the tumor tissue still remains at a low level. Therefore, it is of great scientific significance to fundamentally improve the targeting ability of multifunctional nanocarriers to tumor and to achieve multimodal imaging-guided synergistic cancer therapy. Herein, in this project, we propose to actively actuate magnetic drug nanorobots using external electromagnetic system to achieve precise targeting to tumor site and develop a novel anticancer strategy by fluorescence/T1-T2 MR multimodal imaging-guided combined photothermal-chemotherapy. Firstly, the multifunctional drug nanorobots DOX-Fe3O4@Gd-CPDs could be prepared by Fe3O4 mesoporous magnetic nanoparticles with NIR fluorescent gadolinium doped carbonized polymer dots (Gd-CPDs). Subsequently, under the guiding of fluorescence/T1-T2 MR multimodal imaging, DOX-Fe3O4@Gd-CPDs nanorobots will be directly and precisely delivered to the tumor site by external electromagnetic system, following with the in vivo anticancer study by combined chemotherapy and photothermal therapy on MDA-MB-231 tumor xenografted nude mouse. This study is expected to provide a novel and effective anticancer strategy for direct drug delivery and visualized tumor diagnosis and treatment.

由于人体多重生物学壁垒的阻碍，传统化疗给药途径难以直接到达肿瘤部位。多功能纳米载体虽然一定程度实现了对恶性肿瘤的诊断与治疗，但对肿瘤的靶向效率依然较低。如何从根本上大幅提升纳米药物载体对肿瘤的靶向能力并实现多模态影像导航下的肿瘤联合治疗，对于实现肿瘤的精准诊疗具有重要科学意义。本项目在前期研究基础上拟通过电磁场系统驱动纳米机器人实现对肿瘤部位的精准靶向，并发展荧光/T1-T2 MR多模态影像导航下的化疗与光热介导肿瘤治疗的新策略。首先，拟以多孔Fe3O4纳米粒子偶联近红外荧光钆掺杂碳化聚合物点Gd-CPDs构建纳米机器人DOX-Fe3O4@Gd-CPDs。随后，在荧光/T1-T2 MR成像引导下，利用电磁场系统驱动DOX-Fe3O4@Gd-CPDs精准递送至肿瘤部位，并对MDA-MB-231移植瘤裸鼠模型进行可视化化学-光热治疗，为肿瘤治疗开拓新型高效药物靶向递送与可视化诊疗一体化策略。