Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, School of Basic Medical Sciences, Southern Medical University, 1023 Shatai South Road, Guangzhou, Guangdong, 510515, China.
Biomaterials Research Center, School of Biomedical Engineering, Southern Medical University, 1023 Shatai South Road, Guangzhou, Guangdong, 510515, China.
Small. 2022 Sep;18(35):e2202705. doi: 10.1002/smll.202202705. Epub 2022 Aug 3.
Because of the insufficiency of hydrogen peroxide, the relatively low rate of Fenton reaction, and the active glutathione (GSH) peroxidase 4 (GPX4) in tumor cells, it is difficult to achieve a desirable efficacy of ferroptosis therapy (FT) for tumors based on nanomaterials. Inspired by the concept of "cyclotron" in physics, in this study, a new concept of cycloacceleration of reactive oxygen species (ROS) generation in tumor cells to realize high-performance FT of tumors is proposed. Typically, a magnetic resonance imaging (MRI) contrast agent of dotted core-shell Fe O /Gd O hybrid nanoparticles (FGNPs) is prepared based on exceedingly small magnetic iron oxide nanoparticles (ES-MIONs). Sorafenib (SFN) is loaded and poly(ethylene glycol) methyl ether-poly(propylene sulfide)-NH (mPEG-PPS-NH ) is grafted on the surface of FGNP to generate SA-SFN-FGNP via self-assembly. The results of in vitro and in vivo demonstrate SA-SFN-FGNP can work with the acidic tumor microenvironment and endosomal conditions, Fenton reaction and system X , and generate cyclic reactions in tumor cells, resulting in specific cycloacceleration of ROS generation for high-performance FT of tumors. The very high longitudinal relaxivity (r , 33.43 mM s , 3.0 T) makes sure that the SA-SFN-FGNP can be used for MRI-guided FT of tumors.
由于过氧化氢的不足、芬顿反应的相对较低速率以及肿瘤细胞中活性谷胱甘肽 (GSH) 过氧化物酶 4 (GPX4) 的存在，基于纳米材料难以实现理想的铁死亡治疗 (FT) 效果。受物理“回旋加速器”概念的启发，本研究提出了一种新的肿瘤细胞中活性氧 (ROS) 生成的“回旋加速”概念，以实现肿瘤的高性能 FT。通常，基于非常小的磁性氧化铁纳米粒子 (ES-MIONs) 制备具有点核壳结构的 FeO/GdO 杂化纳米粒子 (FGNPs) 的磁共振成像 (MRI) 造影剂。负载索拉非尼 (SFN) 并在 FGNP 表面接枝聚乙二醇甲基醚-聚丙硫醚-NH(mPEG-PPS-NH)，通过自组装生成 SA-SFN-FGNP。体外和体内结果表明，SA-SFN-FGNP 可以与酸性肿瘤微环境和内体条件、芬顿反应和系统 X 一起工作，并在肿瘤细胞中产生循环反应，从而实现 ROS 生成的特异性回旋加速，以实现肿瘤的高性能 FT。非常高的纵向弛豫率 (r1，33.43 mM s-1，3.0 T) 确保了 SA-SFN-FGNP 可用于 MRI 引导的肿瘤 FT。
