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Natural Killer Cell Membrane-Cloaked Virus-Mimicking Nanogenerator with NIR-Triggered Shape Reversal and •C/•OH Storm for Synergistic Thermodynamic–Chemodynamic Therapy
Advanced Science ( IF 14.3 ) Pub Date : 2021-12-19 , DOI: 10.1002/advs.202103498 Jinyan Lin 1 , Yang Li 1, 2, 3 , Peiyuan Wang 1, 2, 3 , Ming Wu 1 , Fukai Zhu 4 , Yun Zhang 2, 3 , Zhenqing Hou 4 , Jingfeng Liu 1, 2, 3, 5 , Xiaolong Liu 1, 2, 3
Advanced Science ( IF 14.3 ) Pub Date : 2021-12-19 , DOI: 10.1002/advs.202103498 Jinyan Lin 1 , Yang Li 1, 2, 3 , Peiyuan Wang 1, 2, 3 , Ming Wu 1 , Fukai Zhu 4 , Yun Zhang 2, 3 , Zhenqing Hou 4 , Jingfeng Liu 1, 2, 3, 5 , Xiaolong Liu 1, 2, 3
Affiliation
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Free radical-based anticancer modality has been widely applied to cancer therapies. However, it still faces challenges of low delivery efficiency and poor selectivity of free radical generation specifically toward tumors. Herein, a virus-mimicking hollow mesoporous disulfide-bridged organosilica is designed to encapsulate •C precursor 2, 2'-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH), which is then enclosed by tannic acid (TA)/FeIII photothermal assembly and further cloaked by natural killer (NK) cell membrane to achieve synergistic thermodynamic–chemodynamic therapy. The nanogenerator can first evade immune surveillance via NK cell membrane “cloaking” mechanism to strongly accumulate in tumors. Interestingly, the NIR laser-induced heat can trigger NK cell membrane rupture for “shape reversal” to expose a virus-like surface to amplify the cellular uptake, and simultaneously break the azo bonds of AIPH for in situ controlled •C generation. Then upon glutathione (GSH) triggering, the nanogenerator disintegrates via disulfide–thiol exchange and efficiently generates •OH by lysosomal pH-initiated TA-FeIII reaction; notably, the consumption of GSH can amplify oxidative stress to enhance free radical therapy by weakening the self-defense mechanism of tumor cells. It is envisioned that the NK cell membrane-cloaked virus-mimicking and NIR/GSH sequentially activated •C/•OH radical nanogenerator can provide a promising strategy for oxidative stress-based anticancer therapy.
中文翻译：
具有 NIR 触发形状反转和 •C/•OH Storm 协同热力学-化学动力学治疗的自然杀伤细胞膜伪装病毒模拟纳米发电机
基于自由基的抗癌方式已广泛应用于癌症治疗。然而，它仍然面临着递送效率低和特异性针对肿瘤的自由基生成选择性差的挑战。在此，一种模拟病毒的中空介孔二硫键桥接有机硅被设计用于封装 •C 前体 2, 2'-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH)，然后将其包裹在单宁中。酸 (TA)/Fe III光热组装并进一步被自然杀伤（NK）细胞膜掩盖，以实现协同热力学-化学动力学治疗。纳米发电机可以首先通过 NK 细胞膜“隐形”机制逃避免疫监视，从而在肿瘤中强烈积聚。有趣的是，NIR 激光诱导的热量可以触发 NK 细胞膜破裂以进行“形状反转”以暴露病毒样表面以放大细胞摄取，同时破坏 AIPH 的偶氮键以原位控制生成 C。然后在谷胱甘肽 (GSH) 触发时，纳米发电机通过二硫化物-硫醇交换分解，并通过溶酶体 pH 引发的 TA-Fe III有效生成 •OH反应; 值得注意的是，谷胱甘肽的消耗可以放大氧化应激，通过削弱肿瘤细胞的自我防御机制来增强自由基治疗。可以预见，NK细胞膜伪装病毒模拟和NIR/GSH顺序激活•C/•OH自由基纳米发生器可以为基于氧化应激的抗癌治疗提供有前景的策略。
更新日期：2021-12-19
中文翻译：
具有 NIR 触发形状反转和 •C/•OH Storm 协同热力学-化学动力学治疗的自然杀伤细胞膜伪装病毒模拟纳米发电机
基于自由基的抗癌方式已广泛应用于癌症治疗。然而，它仍然面临着递送效率低和特异性针对肿瘤的自由基生成选择性差的挑战。在此，一种模拟病毒的中空介孔二硫键桥接有机硅被设计用于封装 •C 前体 2, 2'-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH)，然后将其包裹在单宁中。酸 (TA)/Fe III光热组装并进一步被自然杀伤（NK）细胞膜掩盖，以实现协同热力学-化学动力学治疗。纳米发电机可以首先通过 NK 细胞膜“隐形”机制逃避免疫监视，从而在肿瘤中强烈积聚。有趣的是，NIR 激光诱导的热量可以触发 NK 细胞膜破裂以进行“形状反转”以暴露病毒样表面以放大细胞摄取，同时破坏 AIPH 的偶氮键以原位控制生成 C。然后在谷胱甘肽 (GSH) 触发时，纳米发电机通过二硫化物-硫醇交换分解，并通过溶酶体 pH 引发的 TA-Fe III有效生成 •OH反应; 值得注意的是，谷胱甘肽的消耗可以放大氧化应激，通过削弱肿瘤细胞的自我防御机制来增强自由基治疗。可以预见，NK细胞膜伪装病毒模拟和NIR/GSH顺序激活•C/•OH自由基纳米发生器可以为基于氧化应激的抗癌治疗提供有前景的策略。
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