Anti-VEGFR2-labeled Enzyme-Immobilized Metal-Organic Frameworks for Tumor Vasculature Targeted Catalytic Therapy
Anti-VEGFR2-labeled Enzyme-Immobilized Metal-Organic Frameworks for Tumor Vasculature Targeted Catalytic Therapy
复制标题
用于肿瘤血管靶向催化治疗的抗 VEGFR2 标记酶固定金属有机框架
DOI：
10.1016/j.actbio.2022.01.037
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发表时间：
2022
影响因子：
9.7
通讯作者：
Biu-wu Bian
中科院分区：
文献类型：
--
作者：
Jingrong Zhou;Kai Wang;Shuaishuai Ding;Lijuan Zeng;Jingya Miao;Yuhua Cao;Xiao Zhang;Gan Tian;Biu-wu Bian
血管生成抑制剂或血管阻断剂的肿瘤血管靶向治疗为肿瘤治疗提供了一条重要的新途径。在这项工作中，通过与铁基金属有机骨架（Fe-MOF）修饰的葡萄糖氧化酶（GOD）偶联抗-GOD酶可催化肿瘤内葡萄糖分解，引发肿瘤饥饿，但提供丰富的过氧化氢作为底物Fe-MOF催化的Fenton样反应产生足够的高毒性羟基自由基用于增强化学动力学治疗，并立即攻击肿瘤血管内皮细胞以破坏现有的血管系统，而抗VEGFR 2抗体引导纳米杂交物靶向血管并阻断VEGF-VEGFR 2连接以防止血管生成。体外和体内实验结果均表明，该纳米复合物可诱导肿瘤细胞凋亡和血管破坏，并在A549荷瘤小鼠模型中表现出增强的肿瘤消退。本研究表明协同靶向肿瘤生长及其血管网络将更有希望用于治疗实体瘤。意义声明协同破坏肿瘤细胞和肿瘤血管为肿瘤治疗提供了潜在的途径。在此前提下，通过与葡萄糖氧化酶的级联反应，开发了一种用于增强肿瘤消融并伴有肿瘤血管破坏和新的血管生成抑制的肿瘤特异性催化纳米药物，所述葡萄糖氧化酶修饰在铁基金属有机框架表面并偶联VEGFR 2抗体。所得数据表明，靶向肿瘤生长及其脉管系统的治疗方案，同时破坏现有脉管系统和抑制新生脉管系统，将更有可能完全根除肿瘤。
Tumor vasculature-targeting therapy either using angiogenesis inhibitors or vascular disrupting agents offers an important new avenue for cancer therapy. In this work, a tumor-specific catalytic nanomedicine for enhanced tumor ablation accompanied with tumor vasculature disruption and angiogenesis inhibition was developed through a cascade reaction with enzyme glucose oxidase (GOD) modified on Fe-based metal organic framework (Fe-MOF) coupled with anti-VEGFR2.The GOD enzyme could catalyze the intratumoral glucose decomposition to trigger tumor starvation and yet provide abundant hydrogen peroxide as the substrate for Fenton-like reaction catalyzed by Fe-MOF to produce sufficient highly toxic hydroxyl radicals for enhanced chemodynamic therapy and instantly attacked tumor vascular endothelial cells to destroy the existing vasculature, while the anti-VEGFR2 antibody guided the nanohybrids to target blood vessels and block the VEGF-VEGFR2 connection to prevent angiogenesis. Bothin vitroandin vivoresults demonstrated the smart nanohybrids could cause the tumor cell apoptosis and vasculature disruption, and exhibited enhanced tumor regression in A549 xenograft tumor-bearing mice model. This study suggested that synergistic targeting tumor growth and its vasculature network would be more promising for curing solid tumors.Statement of significanceCooperative destruction of tumor cells and tumor vasculature offers a potential avenue for cancer therapy. Under this premise, a tumor-specific catalytic nanomedicine for enhanced tumor ablation accompanied with tumor vasculature disruption and new angiogenesis inhibition was developed through a cascade reaction with glucose oxidase modified on the surface of iron-based metal organic framework coupled with VEGFR2 antibody. The resulting data demonstrated that a therapeutic regimen targeting tumor growth as well as its vasculature with both existing vasculature disruption and neovasculature inhibition would be more potential for complete eradication of tumors.