Efficient Polysulfide-Based Nanotheranostics for Triple-Negative Breast Cancer: Ratiometric Photoacoustics Monitored Tumor Microenvironment-Initiated H2S Therapy
Efficient Polysulfide-Based Nanotheranostics for Triple-Negative Breast Cancer: Ratiometric Photoacoustics Monitored Tumor Microenvironment-Initiated H2S Therapy
复制标题
用于三阴性乳腺癌的高效多硫化物纳米治疗：比例光声监测肿瘤微环境引发的 H2S 治疗
DOI：
10.1002/smll.202002939
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发表时间：
2020-09-02
期刊：
影响因子：
13.3
通讯作者：
Huang, Wei
中科院分区：
文献类型：
--
作者：
Li, Jie;Li, Xiang;Huang, Wei
三阴性乳腺癌（TNBC）的发病率难以预测，TNBC在全球女性中的死亡率很高。在这项研究中，开发了一种用于TNBC的治疗诊断方法，其具有比率光声监测硫醇引发的硫化氢（H2S）治疗。将比率光声（PA）探针（CY）与硫醇引发的H2S供体（PSD）整合以形成纳米系统（CY-PSD纳米颗粒）。在这种治疗诊断方法中，CY基于比率PA信号感测PSD产生的H2S，同时精确定位肿瘤区域。此外，H2S对TNBC细胞（MDA-MB 231）具有细胞毒性，显示出63%的肿瘤抑制率。为了进一步验证其药理学机制，对CY-PSD纳米颗粒治疗的肿瘤进行蛋白质组学分析。线粒体功能障碍通过抑制能量供应和启动凋亡而杀死细胞。此外，观察到的氧化应激抑制也产生细胞毒性。发现与TNBC相关的重要京都基因百科全书基因组途径被抑制。这种H2S治疗诊断学方法更新了目前的抗癌疗法，为患有恶性乳腺癌的妇女带来了希望。
The incidence of triple-negative breast cancer (TNBC) is difficult to predict, and TNBC has a high mortality rate among women worldwide. In this study, a theranostics approach is developed for TNBC with ratiometric photoacoustic monitored thiol-initiated hydrogen sulfide (H2S) therapy. The ratiometric photoacoustic (PA) probe (CY) with a thiol-initiated H2S donor (PSD) to form a nanosystem (CY-PSD nanoparticles) is integrated. In this theranostics approach, H2S generated from PSD is sensed by CY based on ratiometric PA signals, which simultaneously pinpoints the tumor region. Additionally, H2S is cytotoxic toward TNBC cells (MDA-MB 231), showing a tumor inhibition rate of 63%. To further verify its pharmacological mechanism, proteomics analysis is performed on tumors treated with CY-PSD nanoparticles. Cells are killed by the significant mitochondrial dysfunction via supressed energy supply and apoptosis initiation. Besides, the observed inhibition of oxidative stress also generates the cytotoxicity. Significant Kyoto Encyclopedia of Genes Genomes pathways related to TNBC are found to be inhibited. This H2S theranostics approach updates the current anticancer therapies which brings promise for women suffering malignant breast cancer.