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首页> 外文期刊>Advanced Functional Materials >Engineering a Therapy-Induced 'Immunogenic Cancer Cell Death' Amplifier to Boost Systemic Tumor Elimination
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Engineering a Therapy-Induced 'Immunogenic Cancer Cell Death' Amplifier to Boost Systemic Tumor Elimination

机译：工程治疗诱导的“免疫原性癌细胞死亡”放大器，以提高全身肿瘤消除

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Immunogenic cancer cell death (ICD) is drawing worldwide attention as it allows dying cancer cells to regulate the host's anti-tumor immune system and awaken immunosurveillance. Thus, effectively activating therapy-induced ICD is of great clinical significance to raise systemic anti-tumor immunity and eradicate post-treatment/abscopal cancer tissues. Enhanced cytotoxic reactive oxygen species (ROS) generation in cancer therapy has been positively correlated to ICD induction, which inspires design of a therapy-induced ICD amplifier. The nanohybrid amplifier (FeOOH@STA/Cu-LDH) is devised based on Cu-containing layered double hydroxide (Cu-LDH), incorporating ROS inducer (FeOOH nanodots), ROS generation booster (Cu-LDH for photothermal therapy), and heat shock protein inhibitor (STA). Treating 4T1 tumor cells with this amplifier translocates calreticulins (CRT, one of main ICD signals) on the surface of dying cancer cells, which achieves the maximum at fever-type temperature (40-42 degrees C). To demonstrate immunotherapeutic efficacy of this nanohybrid, 4T1 tumor-bearing mouse model is established with primary and abscopal tumors. Significantly, only one treatment with the ICD amplifier eradicates the primary tumor and inhibits the abscopal tumor growth upon fever-type heating and induces more cytotoxic T lymphocytes in abscopal tumors and spleens after treatment for 1 week. This research thus provides a new insight into nanomaterial-mediated tumor immunotherapy.
机译：免疫原性癌细胞死亡（ICD）在全世界的关注中绘制，因为它允许染色癌细胞调节宿主的抗肿瘤免疫系统并唤醒免疫尿失度。因此，有效地激活治疗诱导的ICD具有巨大的临床意义，以提高全身的抗肿瘤免疫，并消除治疗后/俯视癌组织。癌症治疗中增强的细胞毒性反应性氧物质（ROS）与ICD诱导呈正相关，其激发了诱导的ICD放大器的设计。基于含Cu的层状双氢氧化物（Cu-LDH），设计了纳米冬小放放大器（FeOOH @ STA / Cu-LDH），其掺入ROS诱导剂（FeOOH纳米液），ROS生成增压器（Cu-LDH用于光热疗法）和热量休克蛋白抑制剂（STA）。用该放大器将4T1肿瘤细胞转化在染色癌细胞表面上的钙化蛋白（CRT，主要ICD信号之一），其在发热型温度（40-42℃）的最大值上。为了证明该纳米冬小化的免疫治疗效果，用原发性和俯视肿瘤建立了4T1肿瘤小鼠模型。值得注意的是，用ICD放大器只有一种处理消除了原发性肿瘤，并抑制了发热型加热时的俯冲肿瘤生长，并在治疗后诱导腹腔肿瘤和脾脏中的更多细胞毒性T淋巴细胞。因此，该研究提供了对纳米材料介导的肿瘤免疫疗法的新洞察力。

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