Engineering Oxygen-Irrelevant Radical Nanogenerator for Hypoxia-Independent Magnetothermodynamic Tumor Nanotherapy
Engineering Oxygen-Irrelevant Radical Nanogenerator for Hypoxia-Independent Magnetothermodynamic Tumor Nanotherapy
复制标题
工程与氧无关的自由基纳米发生器用于缺氧无关的磁热动力肿瘤纳米治疗
DOI：
10.1002/smtd.202001087
复制
发表时间：
2021-01-18
期刊：
影响因子：
12.4
通讯作者：
Huang, Beijian
中科院分区：
文献类型：
--
作者：
Shen, Yujia;Dong, Caihong;Huang, Beijian
肿瘤缺氧大大降低了氧相关治疗方式的治疗效果，因为氧相关抗癌方式中活性氧的产生高度依赖于肿瘤组织中的氧水平。本文提出了一种独特的磁热力学抗癌策略，该策略利用由磁热分解引发剂产生的与氧无关的自由基在体外诱导癌细胞凋亡并在体内抑制肿瘤。自由基纳米发生器是通过在超顺磁性锰和共掺杂纳米粒子（MnFe2O4@CoFe2O4，表示为Mag）表面的介孔二氧化硅涂层的原位工程构建而成的，具有多功能性，其中介孔结构为有效加载引发剂提供了储层，Mag核心在交变磁场（AMF）驱动下作为原位热源。暴露于外源性AMF后，超顺磁芯的磁热疗效应导致负载/递送引发剂（AIPH）快速分解，产生与氧无关的自由基。在低氧肿瘤微环境下，AMF驱动下的磁热效应和有毒自由基的产生在促进癌细胞死亡和抑制肿瘤方面协同有效。这种自由基纳米发生器的显著治疗效果代表了一种有趣的氧无关纳米平台，用于amf启动的协同癌症治疗。
Tumor hypoxia substantially lowers the treatment efficacy of oxygen-relevant therapeutic modalities because the production of reactive oxygen species in oxygen-relevant anticancer modalities is highly dependent on oxygen level in tumor tissues. Here a distinctive magnetothermodynamic anticancer strategy is developed that takes the advantage of oxygen-irrelevant free radicals produced from magnetothermal decomposable initiators for inducing cancer-cell apoptosis in vitro and tumor suppression in vivo. Free-radical nanogenerator is constructed through in situ engineering of a mesoporous silica coating on the surface of superparamagnetic Mn and Co-doped nanoparticles (MnFe2O4@CoFe2O4, denoted as Mag) toward multifunctionality, where mesoporous structure provides reservoirs for efficient loading of initiators and the Mag core serves as in situ heat source under alternating magnetic field (AMF) actuation. Upon exposure to an exogenous AMF, the magnetic hyperthermia effect of superparamagnetic core lead to the rapid decomposition of the loaded/delivered initiators (AIPH) to produce oxygen-irrelevant free radicals. Both the magnetothermal effect and generation of toxic free radicals under AMF actuation are synergistically effective in promoting cancer-cell death and tumor suppression in the hypoxic tumor microenvironment. The prominent therapeutic efficacy of this radical nanogenerator represents an intriguing paradigm of oxygen-irrelevant nanoplatform for AMF-initiated synergistic cancer treatment.