Biomimetic Yolk-Shell Nanocatalysts for Activatable Dual-Modal-Image-Guided Triple- Augmented Chemodynamic Therapy of Cancer
Biomimetic Yolk-Shell Nanocatalysts for Activatable Dual-Modal-Image-Guided Triple- Augmented Chemodynamic Therapy of Cancer
复制标题
用于可激活双模态图像引导三重增强癌症化学动力学治疗的仿生蛋黄壳纳米催化剂
DOI：
10.1021/acsnano.2c08077
复制
发表时间：
2022-10-31
期刊：
影响因子：
17.1
通讯作者：
Li, Juan
中科院分区：
文献类型：
--
作者：
Pan, Yuanbo;Zhu, Yang;Li, Juan
基于芬顿反应的化学动力学疗法（CDT）利用金属离子将活性较低的过氧化氢（H2 O2）转化为有害性较高的过氧化氢（中心点OH）用于肿瘤治疗，近年来引起了越来越多的关注。然而，CDT基本上受到谷胱甘肽（GSH）对中心点OH的清除作用、低细胞内H2 O2水平和低反应速率的阻碍，导致不令人满意的功效。在此，构建了嵌入葡萄糖氧化酶（GOD）和Dox的癌细胞膜（CM）包裹的Au纳米棒核/介孔MnO 2壳蛋黄-壳纳米催化剂（表示为AMGDC），用于在MRI/派引导下协同三重增强的肿瘤CDT和化疗。利用肿瘤细胞膜的同源粘附和免疫逃逸特性，纳米催化剂可以靶向肿瘤并在肿瘤部位逐渐聚集。对于三重增强的CDT，首先，MnO 2壳与肿瘤内GSH反应生成Mn 2+和谷胱甘肽二硫化物，这实现了芬顿样离子递送和GSH介导的清除作用的减弱，导致GSH耗尽增强的CDT。第二，肿瘤内的葡萄糖可以被GOD氧化为H2 O2和葡萄糖酸，实现补充H2 O2增强的CDT。接下来，在NIR-II中吸收的AuNR在NIR-II激光照射后升高局部肿瘤温度，实现光热增强的CDT。由于MnO 2壳的响应性降解，Dox快速释放用于辅助化疗。此外，GSH激活的派/MRI可用于监测CDT过程。这项研究为增强CDT介导的抗肿瘤疗效提供了一个很好的范例。
Fenton reaction-based chemodynamic therapy ( CDT), which applies metal ions to convert less active hydrogen peroxide (H2O2) into more harmful hydroxyl peroxide (center dot OH) for tumor treatment, has attracted increasing interest recently. However, the CDT is substantially hindered by glutathione (GSH) scavenging effect on center dot OH, low intracellular H2O2 level, and low reaction rate, resulting in unsatisfactory efficacy. Here, a cancer cell membrane (CM)-camouflaged Au nanorod core/mesoporous MnO2 shell yolk-shell nanocatalyst embedded with glucose oxidase (GOD) and Dox (denoted as AMGDC) is constructed for synergistic triple-augmented CDT and chemotherapy of tumor under MRI/PAI guidance. Benefiting from the homologous adhesion and immune escaping property of the cancer CM, the nanocatalysts can target tumor and gradually accumulate in tumor site. For triple-augmented CDT, first, the MnO2 shell reacts with intratumoral GSH to generate Mn2+ and glutathione disulfide, which achieves Fenton-like ion delivery and weakening of GSH-mediated scavenging effect, leading to GSH depletion-enhanced CDT. Second, the intratumoral glucose can be oxidized to H2O2 and gluconic acid by GOD, achieving supplementary H2O2-enhanced CDT. Next, the AuNRs absorbing in NIR-II elevate the local tumor temperature upon NIR-II laser irradiation, achieving photothermal-enhanced CDT. Dox is rapidly released for adjuvant chemotherapy due to responsive degradation of MnO2 shell. Moreover, GSH-activated PAI/MRI can be used to monitor CDT process. This study provides a great paradigm for enhancing CDT-mediated antitumor efficacy.