Hypoxia-Irrelevant Photonic Thermodynamic Cancer Nanomedicine
Hypoxia-Irrelevant Photonic Thermodynamic Cancer Nanomedicine
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DOI：
10.1021/acsnano.8b08910
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发表时间：
2019-02-01
期刊：
影响因子：
17.1
通讯作者：
Chen, Yu
中科院分区：
文献类型：
--
作者：
Xiang, Huijing;Lin, Han;Chen, Yu
缺氧的肿瘤微环境严重降低了依赖氧气的抗癌模式的治疗效果，因为肿瘤缺氧阻碍了有毒活性氧物质的产生。在此我们报道了一种热力学癌症治疗模式，该模式利用从热不稳定引发剂产生的与氧气无关的自由基来诱导癌细胞死亡。通过在二维Nb₂C MXene纳米片表面直接生长介孔二氧化硅层以实现多功能性，设计了一种自由基纳米发生器，其中介孔为引发剂提供了储存空间，而MXene核心在近红外 - II生物窗口（NIR - II）作为光热触发器。在1064 nm NIR - II激光照射下，Nb₂C MXene的光热转换效应促使封装的引发剂（AIPH）快速释放并迅速分解以产生自由基，这在常氧和缺氧微环境中都促进了癌细胞的凋亡。系统的体外和体内评估已经证明了这种有趣的光子纳米平台实现的热力学癌症治疗的协同治疗效果，通过NIR - II激光照射完全根除4T1肿瘤且无复发。这项工作开创了通过在NIR - II生物窗口进行光子触发实现不依赖氧气的癌症治疗的热力学疗法。
The hypoxic tumor microenvironment severely lowers the therapeutic efficacy of oxygen-dependent anticancer modalities because tumor hypoxia hinders the generation of toxic reactive oxygen species. Here we report a thermodynamic cancer-therapeutic modality that employs oxygen-irrelevant free radicals generated from thermo-labile initiators for inducing cancer cell death. A free radical nanogenerator was engineered via direct growth of mesoporous silica layer onto the surface of two-dimensional Nb2C MXene nanosheets toward multifunctionality, where the mesopore provided the reservoirs for initiators and the MXene core acted as the photonic-thermal trigger at the near-infrared-II biowindow (NIR-II). Upon illumination by a 1064 nm NIR-II laser, the photothermal-conversion effect of Nb2C MXene induced the fast release and quick decomposition of the encapsulated initiators (AIPH) to produce free radicals, which promoted cancer cell apoptosis in both normoxic and hypoxic microenvironment. Systematic in vitro and in vivo evaluations have demonstrated the synergistic-therapeutic outcome of this intriguing photonic nanoplatform-enabled thermodynamic cancer therapy for completely eradicating the 4T1 tumors without recurrence by NIR-II laser irradiation. This work pioneers the thermodynamic therapy for oxygen-independent cancer treatment by photonic triggering at the NIR-II biowindow.