Shen Jinchao, Rees Thomas W, Zhou Zhiguo, Yang Shiping, Ji Liangnian, Chao Hui
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275, PR China.
The Education Ministry Key Lab of Resource Chemistry and Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai, 200234, PR China.
Biomaterials. 2020 Aug;251:120079. doi: 10.1016/j.biomaterials.2020.120079. Epub 2020 Apr 29.
Magnetic hyperthermia therapy (MHT) and chemodynamic therapy (CDT) are non-invasive in situ treatments without depth limitations and with minimum adverse effects on surrounding healthy tissue. We herein report a mitochondria-targeting magnetothermogenic nanozyme (Ir@MnFeO NPs) for highly efficient cancer therapy. An iridium(III) complex (Ir) acts as a mitochondria-targeting agent on the surface of MnFeO NPs. On exposure to an alternating magnetic field (AMF), the Ir@MnFeO NPs induce a localized increase in temperature causing mitochondrial damage (MHT effect). Meanwhile glutathione (GSH) reduces Fe(III) to Fe(II) on the NPs surface, which in turn catalyzes the conversion of HO to cytotoxic •OH (CDT effect). The depletion of GSH (a •OH scavenger) increases CDT efficacy, while the localized increase in temperature increases the rate of conversion of both Fe(III) to Fe(II) and HO to •OH further enhancing the CDT effect. In addition, the disruption of cellular redox homeostasis due to CDT, leads to greater sensitivity of the cell towards MHT. This nanoplatform integrates these excellent therapeutic properties, with two-photon microscopy (TPM) (demonstrated in vitro) and magnetic resonance imaging (MRI) (demonstrated in vivo) to enable the precise and effective treatment of cancer.
磁热疗（MHT）和化学动力疗法（CDT）是无创原位治疗方法，没有深度限制，对周围健康组织的副作用最小。我们在此报告一种用于高效癌症治疗的线粒体靶向磁热纳米酶（Ir@MnFeO NPs）。铱（III）配合物（Ir）在MnFeO NPs表面充当线粒体靶向剂。在暴露于交变磁场（AMF）时，Ir@MnFeO NPs会导致局部温度升高，从而造成线粒体损伤（MHT效应）。同时，谷胱甘肽（GSH）将NPs表面的Fe（III）还原为Fe（II），进而催化HO转化为细胞毒性的•OH（CDT效应）。GSH（一种•OH清除剂）的消耗会提高CDT疗效，而局部温度升高会增加Fe（III）向Fe（II）以及HO向•OH的转化速率，进一步增强CDT效应。此外，CDT导致的细胞氧化还原稳态破坏，会使细胞对MHT的敏感性更高。这种纳米平台整合了这些优异的治疗特性，并结合了双光子显微镜（TPM）（体外证明）和磁共振成像（MRI）（体内证明），以实现对癌症的精确有效治疗。
