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Cycloacceleration of Reactive Oxygen Species Generation Based on Exceedingly Small Magnetic Iron Oxide Nanoparticles for Tumor Ferroptosis Therapy
Small ( IF 13.0 ) Pub Date : 2022-08-03 , DOI: 10.1002/smll.202202705 Huimin Zhou 1, 2 , Xuanyi Lu 2 , Chao Du 3 , Zijian Zhou 3 , Jie Feng 4 , Zhiyu Liang 4 , Yikai Xu 4 , Xiaozhong Qiu 1 , Zheyu Shen 2
Small ( IF 13.0 ) Pub Date : 2022-08-03 , DOI: 10.1002/smll.202202705 Huimin Zhou 1, 2 , Xuanyi Lu 2 , Chao Du 3 , Zijian Zhou 3 , Jie Feng 4 , Zhiyu Liang 4 , Yikai Xu 4 , Xiaozhong Qiu 1 , Zheyu Shen 2
Affiliation
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 Fe3O4/Gd2O3 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)-NH2 (mPEG-PPS-NH2) 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 XC−, 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 (r1, 33.43 mM−1 s−1, 3.0 T) makes sure that the SA-SFN-FGNP can be used for MRI-guided FT of tumors.
中文翻译:
基于极小磁性氧化铁纳米粒子的活性氧生成循环加速用于肿瘤铁死亡治疗
由于过氧化氢不足、芬顿反应速率相对较低以及肿瘤细胞中存在活性谷胱甘肽(GSH)过氧化物酶4(GPX4),因此基于铁死亡疗法(FT)的肿瘤难以达到理想的疗效。纳米材料。受物理学中“回旋加速器”概念的启发,本研究提出了一种新的循环加速肿瘤细胞内活性氧(ROS)生成的概念,以实现肿瘤的高性能FT。通常,点状核壳 Fe 3 O 4 /Gd 2 O 3的磁共振成像 (MRI) 造影剂混合纳米粒子(FGNPs)是基于极小的磁性氧化铁纳米粒子(ES-MIONs)制备的。负载索拉非尼(SFN)并将聚(乙二醇)甲基醚-聚(丙烯硫化物)-NH 2(mPEG-PPS-NH 2)接枝在FGNP表面,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 X C -系统协同作用,在肿瘤细胞中产生循环反应,导致特异性循环加速 ROS 的产生- 肿瘤的性能 FT。非常高的纵向弛豫率 ( r 1 , 33.43 mM -1 s -1, 3.0 T) 确保 SA-SFN-FGNP 可用于 MRI 引导的肿瘤 FT。
更新日期:2022-08-03
中文翻译:
基于极小磁性氧化铁纳米粒子的活性氧生成循环加速用于肿瘤铁死亡治疗
由于过氧化氢不足、芬顿反应速率相对较低以及肿瘤细胞中存在活性谷胱甘肽(GSH)过氧化物酶4(GPX4),因此基于铁死亡疗法(FT)的肿瘤难以达到理想的疗效。纳米材料。受物理学中“回旋加速器”概念的启发,本研究提出了一种新的循环加速肿瘤细胞内活性氧(ROS)生成的概念,以实现肿瘤的高性能FT。通常,点状核壳 Fe 3 O 4 /Gd 2 O 3的磁共振成像 (MRI) 造影剂混合纳米粒子(FGNPs)是基于极小的磁性氧化铁纳米粒子(ES-MIONs)制备的。负载索拉非尼(SFN)并将聚(乙二醇)甲基醚-聚(丙烯硫化物)-NH 2(mPEG-PPS-NH 2)接枝在FGNP表面,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 X C -系统协同作用,在肿瘤细胞中产生循环反应,导致特异性循环加速 ROS 的产生- 肿瘤的性能 FT。非常高的纵向弛豫率 ( r 1 , 33.43 mM -1 s -1, 3.0 T) 确保 SA-SFN-FGNP 可用于 MRI 引导的肿瘤 FT。