多靶点靶向与多模态成像引导的肿瘤磁感应热疗及协同效应研究

Targeted multi-modal imaging-mediated accurate therapy in vivo is future development direction of individualized precision medicine field. As the conventional passively-targeted magnetic resonance imaging (MRI) contrast agents and efficient magnetic-induced heating agents, magnetic nanoparticles (MNPs) have widely received enormous attention in clinical applications based on their unique functional properties and excellent biocompatibility. However, it has rather challenging in MNPs-mediated active targeted magnetic hyperthermia therapy by intravenously administration in vivo and their further enhanced therapy efficacy. In this regard, several basic scientific issues and key factors, such as the improved monodispersity of MNPs and their magnetic-induced heating effect, the increased MNPs accumulation in target tissues, the synergistic hyperthermia and chemotherapy effect, the focused heat induction and the multi-modal imaging-guided precise diagnostics, should be especially considered. In our project, we proposed a drug-loaded magnetic lipid nanoparticle probes-mediated simple, safe, effective and broad-spectrum multi-targeted targeting (e.g., tumor angiogenesis and glucose metabolism) and in vivo multi-modal imaging (e.g., MRI, fluorescence imaging and infrared-thermal imaging) platform here based on our previous research. We will discuss the regulation of tumor multi-targeted targeting and multi-modal imaging, promote the cancer therapy combining hyperthermia and chemotherapy based on the magnetic-induced heating effect of MNPs and magnetic-induced drug delivery, and the nanoparticle peroxidase-like activity simulated catalysis induced cytotoxicity, finally achieving the targeted multi-modal imaging-guided cancer synergistic therapy.

靶向多模影像指导的精准治疗是未来个体化精准医学的发展方向。磁性纳米材料由于独特的多功能特性和优秀的生物相容性，作为被动靶向磁共振造影剂和介入给药磁感应热疗制剂已经在临床上获得应有。但是，如何实现经静脉主动靶向磁感应热疗并进一步提升治疗效果面临着重大挑战，这需要进一步提升纳米颗粒的单分散性和交流磁热效应、增加靶组织靶细胞累积、联合多机制协同杀伤、聚焦磁感应加热以及依赖于多模成像的精确指导，其中蕴藏的基础科学问题和关键核心技术急需突破。本项目在多年研究基础上提出构建一种简单、安全、有效、广谱的多靶点靶向（肿瘤新生血管和葡萄糖代谢）和多模态成像（磁共振/荧光/热成像）的磁性载药脂质纳米探针平台，探讨其肿瘤多靶点靶向与多模成像的调控规律，并基于纳米探针磁感应热疗效应、磁控药物释放效应及过氧化物模拟酶的细胞毒作用，联合化疗进行多机制协同治疗，最终实现靶向多模态成像精确指导的磁感应热协同治疗。

靶向多模影像指导的精准治疗是未来个体化精准医学的发展方向。磁性纳米材料由于独特的多功能特性和优秀的生物相容性，作为被动靶向磁共振造影剂和介入给药磁感应热疗制剂已经在临床上获得应有。但是，如何实现经静脉主动靶向磁感应热疗并进一步提升治疗效果面临着重大挑战，这需要进一步提升纳米颗粒的单分散性和交流磁热效应、增加靶组织靶细胞累积、联合多机制协同杀伤、聚焦磁感应加热以及依赖于多模成像的精确指导，其中蕴藏的基础科学问题和关键核心技术急需突破。本项目在磁性纳米颗粒控制制备的基础上，构建了一种多靶点靶向（肿瘤新生血管和葡萄糖代谢）和多模态成像（磁共振/荧光/热成像）的磁性载药脂质纳米探针平台和智能凝胶平台，探讨了肿瘤多靶点靶向与多模成像的调控规律，并基于纳米颗粒磁感应热疗效应、磁控药物释放效应及过氧化物模拟酶的细胞毒作用，联合化疗进行多机制协同治疗，最终实现了多模态成像精确指导的磁感应热协同治疗。