介孔Fe/Fe3O4蛋黄/蛋壳结构的构建及其微环境响应释放零价铁用于MRI指导肿瘤治疗

基于铁的芬顿反应及其诱导的细胞死亡为癌症治疗提供了新策略。氧化铁纳米材料具有优越的生物相容性及靶向性。但其主要依赖Fe2+的芬顿反应，在肿瘤病灶反应效率低，无法单独用于治疗，多与其他药物联用。零价铁的类芬顿反应活性高，但极易氧化丧失活性。本课题拟开发介孔Fe/Fe3O4蛋黄/蛋壳结构（PYSNPs）作为零价铁智能递送系统：正常生理环境下，氧化铁壳保护Fe核不被氧化并掩盖其活性；肿瘤微酸环境，介孔层刻蚀破碎，Fe核暴露高效促进ROS产生，杀伤肿瘤细胞；最终代谢为生物安全的铁离子。通过表面修饰提高其生物相容性及Fe释放的可控性。利用其磁学性质，对其磁导以提高肿瘤蓄积；通过MRI实现诊断定位、监测Fe释放及疗效评估；利用磁流体热疗辅助治疗。该项目开发的PYSNPs将提供一种肿瘤选择性强、生物安全性好、组成简单的Fe(0)载体，在较小剂量下，无需装载其他药物，实现影像指导下的肿瘤治疗。

The iron-based Fenton reaction and its induced cell death provide a new strategy for cancer treatment. Iron oxide nanomaterials have excellent biocompatibility and tumor targeting capability. However, Fe2+ involved Fenton reaction is inefficient in the weak acidic tumor microenvironment for directly treatment, and thus, iron oxide nanomaterials need to work synergistically with other drugs. Zero-valent iron is known to be highly active in Fenton-like reaction. But, they are very easy to be oxidized into iron oxide and lose their activity. We proposed to develop a novel porous Fe/Fe3O4 yolk-shell nanoparticles (PYSNPs) as an intelligent delivery system for zero-valent iron: under normal physiological environment, the iron oxide shell protects Fe core from oxidation and covers up its activity; in the weak acidic tumor microenvironment, the porous shell will be etched and break, and the exposure of the Fe core will effectively cause ROS production to induce cell death; the final product is iron ions which are biocompatible. The further surface modification of PYSNPs will improve their biocompatibility and the controllability of Fe(0) release. Making use of their excellent magnetic properties, external magnetic field will be employed in order to enhance their tumor accumulation. MRI will enable the early diagnosis of tumor, real-time monitoring of the release process of Fe as well as the curative effect. In short, the PYSNPs we developed will provide a simple and clear zero-valent iron carrier with superior tumor selectivity and good biosafety. Without the help of other drugs, a small dose of PYSNPs will enable imaging guided tumor therapy.