An ER-Horse Detonating Stress Cascade for Hepatocellular Carcinoma Nanotherapy.
An ER-Horse Detonating Stress Cascade for Hepatocellular Carcinoma Nanotherapy.
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DOI：
10.1021/acsnano.2c11922
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发表时间：
2023-02
期刊：
影响因子：
17.1
通讯作者：
X. Bian;Ningke Fan;Meng Li;Daobin Han;Jia Li;Lu Fan;Xinyu Li;Liangsheng Kong;Hua Tang;Shi-jia Ding;Fangzhou Song;Siqiao Li;W. Cheng
中科院分区：
文献类型：
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作者：
X. Bian;Ningke Fan;Meng Li;Daobin Han;Jia Li;Lu Fan;Xinyu Li;Liangsheng Kong;Hua Tang;Shi-jia Ding;Fangzhou Song;Siqiao Li;W. Cheng
持续和过度的内质网应激（ERS）可引起细胞快速凋亡。ERS信号传导的治疗性干扰为癌症纳米治疗提供了巨大的潜力。在本文中，已经开发了用于精确HCC纳米治疗的包封siGRP 94的肝细胞癌（HCC）细胞衍生的ER囊泡（ERV），表示为ER-马。简单地说，ER-马像特洛伊木马一样，通过同型伪装被识别，模仿ER的生理功能，并外源性地打开Ca 2+通道。因此，细胞外Ca 2+的强制性灌注触发了加重的应激级联（ERS和氧化应激）和凋亡途径，并通过siGRP 94抑制未折叠蛋白反应。总的来说，我们的研究结果为通过ERS信号干扰进行有效的HCC纳米治疗提供了一个范例，并探索了精确癌症治疗的生理信号转导途径的治疗干扰。
Persisting and excessive endoplasmic reticulum stress (ERS) can evoke rapid cell apoptosis. Therapeutic interference of ERS signaling holds enormous potential for cancer nanotherapy. Herein, a hepatocellular carcinoma (HCC) cell-derived ER vesicle (ERV) encapsulating siGRP94, denoted as ER-horse, has been developed for precise HCC nanotherapy. Briefly, ER-horse, like the Trojan horse, was recognized via homotypic camouflage, imitated the physiological function of ER, and exogenously opened the Ca2+ channel. Consequently, the mandatory pouring-in of extracellular Ca2+ triggered the aggravated stress cascade (ERS and oxidative stress) and apoptosis pathway with the inhibition of unfolded protein response by siGRP94. Collectively, our findings provide a paradigm for potent HCC nanotherapy via ERS signaling interference and exploring therapeutic interference of physiological signal transduction pathways for precision cancer therapy.