二硫化钼/贵金属纳米复合材料的制备及其在肿瘤多模式治疗中的应用研究

Since the discovery of graphene, novel two-dimensional (2D) nanomaterials have been receiving great attention in recent years due to their unique properties.2D nanomaterials can be used as an ideal substrate for fabrication of functional nanocomposite materials. The property of strong NIR absorbance makes them a promising candidate for photothermal therapy and the extraordinary surface-area-to-mass ratio of 2D nanosheets enables highly efficient drug loading as drug delivery systems.This topic will focus on the fabrication of Molybdenum disulfide (MoS2)/noble metal nanocomposite materials by laser ablation of noble metal target in MoS2 nanosheets solutions. We will investigate the effects of laser parameters and different kinds of noble metal nanoparticles on the synthesis of nanocomposite materials. And then we will modify MoS2/noble metal nanocomposite materials with PEG and target agents to improve the stability and compatibility in physiological environments. We will further investigate the mechanism of cell uptake for enhancing the bioavailability of MoS2/noble metal nanocomposite materials. Finally, combining the properties of ultrahigh surface-to-volume ratios for drug delivery and strong absorbance in the NIR region for photothermal therapy, our work will highlight the promise of using MoS2/noble metal nanocomposite materials as a novel nanoscale multimodal platform for cancer therapy, and encourage further in-depth investigations the therapeutic value of this novel type of 2D nanocomposite materials .

继石墨烯之后，新型二维层状材料的开发和探索成为新的研究热点。二维材料因其优异的平面片层结构在功能复合材料的制备中可以作为理想的载体，其独特的光学性能及较大的比表面积在生物医学领域尤其是光热治疗及药物递送等领域也将引起广泛关注。本课题以二维层状材料二硫化钼为研究对象，拟应用液相激光烧蚀技术，研究不同种类贵金属纳米颗粒以及不同激光参数在功能复合材料制备中的影响，一步法制备体系纯净的二硫化钼/贵金属功能纳米复合材料。在此基础上，拟进一步对功能复合材料进行表面改性和靶向修饰，检测其在生物体内的稳定性和生物相容性,研究其被细胞摄取的效率和机理，以提高其生物利用率。同时利用二硫化钼比表面积大的特点负载抗肿瘤药物以及在近红外区域高吸收的特性，拟开发一种集靶向，成像，化疗，热疗一体化的肿瘤治疗平台，并对其疗效进行评价，探讨其在肿瘤治疗中的潜在应用前景。

单层或少数层二硫化钼片层结构是一种新型的二维材料，其优异的物理化学性质引起了研究者的广泛关注。本研究首先制备了二硫化钼片层结构，进一步将具有免疫佐剂功能的寡核苷酸CpG修饰在二硫化钼片层表面，得到一种新型片层二硫化钼基纳米佐剂。新型片层二硫化钼基纳米免疫佐剂粒径小、尺寸均一，生物相容性好。相比单独CpG, 二硫化钼片层结构能够对CpG起到很好的保护作用，免受DNA酶的降解，增强其在生理环境下的稳定性。二硫化钼片层结构还可以增强巨噬细胞对CpG的摄取效率，利用其较强的光热转换效率，可进一步增加CpG在细胞内的蓄积水平以及在体内的释放。最终显著提高了免疫刺激因子如TNF-α, IL-6, IL-12等的表达和分泌，促进了树突状细胞的成熟，提高了免疫应答。同时，联合近红外光照射，二硫化钼基纳米佐剂还能够刺激巨噬细胞对相关肿瘤细胞的杀伤效果，实现对肿瘤细胞的免疫治疗，并对相关机理进行了探讨。