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CuS-NiS 纳米材料用于 MRI 引导的胃癌光热治疗 触发线粒体介导的细胞凋亡和 MLKL/CAPG 介导的坏死性凋亡。

CuS-NiS nanomaterials for MRI guided phototherapy of gastric carcinoma triggering mitochondria-mediated apoptosis and MLKL/CAPG-mediated necroptosis.

机构信息

Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, China.

The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, China.

出版信息

Nanotoxicology. 2020 Aug;14(6):774-787. doi: 10.1080/17435390.2020.1759727. Epub 2020 May 13.

Abstract

Gastric carcinoma is one of the most lethal malignant tumors. As part of our long-term efforts on seeking effective diagnosis and therapeutic strategies of gastric cancer, we present herein novel ternary copper-based chalcogenide nanoplatform CuS-NiS nanomaterials with outstanding photothermal (PT)/photodynamic (PD) property that could effectively suppress human gastric cancer and vo without obvious side effects. We revealed that CuS-NiS induced reactive oxygen species (ROS) generation, leading to apoptosis through Bcl-2/Bax pathway of human gastric cancer cells under 808 nm near-infrared (NIR) irradiation. In addition, we also confirmed that the combination of CuS-NiS and 808 nm NIR laser treatment triggered necroptosis by regulating the novel pathway MLKL/CAPG of human gastric cancer cells. Moreover, the CuS-NiS exhibited excellent contrast enhancement according to magnetic resonance imaging (MRI). Taken together, we reported new ternary copper-based chalcogenide nanomaterials CuS-NiS, which could be successfully applied for MRI-guided PT/PD therapy of gastric carcinoma through mitochondria-mediated apoptosis and MLKL/CAPG-mediated necroptosis.

摘要

胃癌是最致命的恶性肿瘤之一。作为我们长期寻求有效胃癌诊断和治疗策略的努力的一部分,我们在此提出了具有优异光热(PT)/光动力(PD)性能的新型三元铜基硫属化物纳米平台 CuS-NiS 纳米材料,可有效抑制人胃癌和 vo,且无明显副作用。我们揭示了 CuS-NiS 在 808nm 近红外(NIR)照射下通过 Bcl-2/Bax 通路诱导人胃癌细胞产生活性氧(ROS),从而导致细胞凋亡。此外,我们还证实 CuS-NiS 和 808nm NIR 激光联合处理通过调节人胃癌细胞的新型 MLKL/CAPG 通路触发坏死性凋亡。此外,CuS-NiS 根据磁共振成像(MRI)显示出优异的对比增强效果。综上所述,我们报道了新型三元铜基硫属化物纳米材料 CuS-NiS,它可以通过线粒体介导的细胞凋亡和 MLKL/CAPG 介导的坏死性凋亡成功应用于 MRI 引导的胃癌 PT/PD 治疗。

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