Homologous Targeting Cascade Nanobioreactor for Autophagy Inhibition Amplified Tumor Catalytic Therapy
Homologous Targeting Cascade Nanobioreactor for Autophagy Inhibition Amplified Tumor Catalytic Therapy
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DOI：
10.1021/acsmaterialslett.2c00617
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发表时间：
2023-01
影响因子：
11.4
通讯作者：
Xiaodan Wei;Ningxi Li;Honglin Huang;Geng Yang;Hanxi Zhang;Tingting Li;Xiang Qin;Shun Li
中科院分区：
文献类型：
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作者：
Xiaodan Wei;Ningxi Li;Honglin Huang;Geng Yang;Hanxi Zhang;Tingting Li;Xiang Qin;Shun Li
基于精细纳米医学的催化疗法正在成为肿瘤特异性治疗的先驱模式。然而，其治疗效果往往受到癌细胞自噬等自我保护机制的影响。本文开发了一种同源靶向级联纳米生物反应器（asCQ/CuZ@M4T1-G），用于自噬抑制扩增酶- fenton样催化治疗。CQ/CuZ@M4T1-Gwas是由葡萄糖氧化酶（GOx）锚定肿瘤细胞膜负载Cu2+和氯喹（CQ）负载的沸石咪唑盐框架构建的。gox驱动的糖酵解有效地切断了饥饿治疗所需的葡萄糖供应，同时也提供了丰富的h2o2，降低了ph。同时，释放的Cu2+被谷胱甘肽还原为Cu+，并通过Cu+介导的芬顿样反应将升高的h2o2转化为高毒性的·OH。更重要的是，应用自噬抑制剂CQ阻断下游自噬通量，阻碍自我保护途径。因此，肿瘤屈服于酶- fenton样级联反应的严重应激，产生了显著的治疗效果，如体外和体内实验结果所示。我们的研究为未来一种新型肿瘤治疗提供了一种由级联纳米生物反应器介导的有前景的方案。
Catalytic therapy based on elaborate nanomedicine is emerging as a pioneering modality for tumor-specific treatment. However, its therapeutic efficiency is usually compromised by the self-protective mechanism of cancer cells, such as autophagy. Herein, a homologous targeting cascade nanobioreactor (denoted asCQ/CuZ@M4T1-G) was developed for the autophagy inhibition amplified enzymic-Fenton like catalytic therapy.CQ/CuZ@M4T1-Gwas constructed by wearing Cu2+-doped and chloroquine (CQ) loaded zeolitic imidazolate framework with glucose oxidase (GOx) anchored tumor cell membrane. The GOx-driven glycolysis effectively cut off glucose supply for starvation therapy, which also provided abundant H2O2and decreased pH. Meanwhile, the released Cu2+was reduced to Cu+by glutathione and converted the elevated H2O2into highly toxic ·OH via a Cu+-mediated Fenton-like reaction in the tumor. More importantly, autophagy inhibitor CQ was applied to block downstream autophagic flux and hinder the self-protection pathway. Thus, the tumor succumbed to the severe stress of an enzymatic-Fenton like cascading reaction, yielding a remarkable therapeutic effect as demonstrated by bothin vitroandin vivoresults. Our study provides a promising regimen mediated by the cascade nanobioreactor for a new type of oncotherapy in the future.