新型微波肿瘤热疗增敏纳米二硫化钼的设计合成与多功能应用原理研究

Tumor hyperthermia therapy technique based on the properties of interaction between nanomaterials and electromagnetic waves has been developed as a hot research in biomedical field. Due to the special controlled energy gap, molybdenum disulfide (MoS2) nanomaterials will be employed as a novel microwave thermotherapy nanostructure. This program aims to synthesize hollow MoS2 nanospheres with layer structure via ultrafast chemical aerosol flow synthesis method and explore the reaction mechanism. The controlled mechanism between microstructure and physicchemistry properties will be further explored and discussed. Through the optimization process of medical microwave band properties, a kind of novel hollow MoS2 nanospheres with high microwave heat conversion efficiency will be obtained. This program attempts to utilize the novel hollow MoS2 nanospheres as carriers to load Fe3O4 nanoparticles and anti-cancer drugs inside the hollow structure, and to cross-link smart targeting molecule outside the surface. Then a composite nanostructure based on hollow MoS2 nanospheres will be obtained, which owns the abilities of dual-mode tumor microwave heat transferand drug controlled release, dual-mode active and passive targeting, and multi-mode microwave thermotherapy /MRI/CT imaging simultaneously. This will achieve the nano-visual tumor therapy, and provide novel materials and new techniques for targeted and multi-mode imaging-therapy of tumors.

利用纳米材料与电磁波相互作用特性发展的肿瘤热疗技术是当前纳米生物医用热点研究领域，二硫化钼特殊的可调控带隙使其成为极具潜力的新型微波热疗纳米结构。本项目探索二硫化钼合成的反应原理，利用超声雾化技术，快速、连续化制备出具有层状结构的纳米中空二硫化钼球。深入研究其纳微结构与物理化学性质的关系与调控机制，优化其在医用微波波段的吸收特性，构建一种新型高微波-热转换效率的二硫化钼纳米球。利用层状结构中空二硫化钼球的中空结构，在空腔内生长Fe3O4纳米颗粒，并装载抗癌化疗药物，表面修饰主动靶向分子，得到具有微波热转换、化疗药物缓控释双模肿瘤治疗功能，主动与被动靶向功能，微波热疗、MRI影像和CT影像三重肿瘤影像功能的二硫化钼复合纳米结构，为恶性肿瘤的靶向多模式治疗-影像提供新材料、新技术和新思路。

肿瘤边缘加热不充分导致热消融中存在的盲点是微波术后复发率较高的重要原因，热疗增敏材料的研制为解决上述问题提供了有效的策略。但是目前微波增敏材料存在种类缺乏，产率低，热转换效率低的关键问题。本项目深入研究其微纳结构与物化性质的关系与调控机制，利用数字仿真模型，优化其在医用微波波段的吸收特性，构建了一类尺寸可控的新型高微波-热转换效率的二硫化钼以及复合结构的纳米球。研究表明，该复合结构的纳米球对化疗药具有高效的负载，并实现pH以及温度响应的可控释放。细胞和动物模型证明，使用该复合结构的纳米球显著提高了肿瘤微波热疗的消融面积，以及均一性，实现对肿瘤的有效抑制。二硫化钼具有优异的CT成像效果，与磁颗粒的MR成像集合，初步研究实现了具有MR和CT双模影像介导的多功能二硫化钼纳米复合材料对肿瘤的有效诊断和治疗，为精准微波热消融提供了实验依据和奠定理论基础。本项目按照研究计划的路线、方案完成了项目的既定目标，取得了一系列有意义的研究成果，推动了纳米制剂以及纳米药物载体材料向临床的应用。