新型AuNC@Fe3O4造影剂用于肝癌靶向T1、T2-MRI/CT成像及增敏化疗药物的效应和机制研究

近年来随着MRI/CT多模成像的诊断技术及设备的高度发展，人们迫切需要开发与之相对应的多模态造影剂用于肿瘤的精确诊断和辅助治疗。本项目基于对超小四氧化三铁（Fe3O4≤3nm）和金笼状纳米粒子（AuNC）的研究基础，结合靶向分子修饰技术，拟合成一种新型多模态造影剂（AuNC@Fe3O4）用于肿瘤的靶向T1-T2模式MRI 和 CT成像。由于细胞自噬是纳米材料的一种标志性生物效应，且在预实验中我们首次发现AuNC@Fe3O4能够明显诱发HepG2细胞自噬并引起AMPK和mTOR蛋白活性变化，因此本项目拟系统研究AuNC@Fe3O4诱导细胞自噬的效应和分子机制，并进一步探讨AuNC@Fe3O4诱发的自噬效应用于化疗药物增敏的辅助治疗应用。本项目的研究将为新一代造影剂在多模态诊断与辅助治疗领域中的开发和应用提供新的思路和方法。

In the recent year, accompanied with the development of multimodal imaging diagnosis technology and devices, it is highly demanded to explore appropriate multimodal contrast agents (MCAs) for accurate diagnosis and adjuvant therapy. Here a novel MCAs (AuNC@Fe3O4) will be synthesized based on ultra-small iron oxide nanoparticles (Fe3O4≤3nm), Au nanocages (Au NC) and targeting molecular modification techniques for tumor simultaneous T1 -T2 MRI and CT contrast imaging. Since autophagy is one of typical biological effects of nanomaterials, and we first found that AuNC@Fe3O4 could significantly induce autophagy in HepG2 cells and cause protein activity changes of AMPK and mTOR in the pre-experiment, so we also intent to systematically study the effect and molecular mechanisms of autophagy induced by AuNC@Fe3O4, and to further explore the effect of induced autophagy on sensitization chemotherapeutics to achieve adjuvant therapy. The work in this project will give new ideas and methods for the development and application of new generation of contrast agents for multimodal imaging diagnosis and adjuvant therapy.