改善纳米药物Basolite F-300@GOD@anti-VEGFR2的肿瘤微血管通透性以增强胶质瘤疗效
结题报告
批准号:
81903100
项目类别:
青年科学基金项目
资助金额:
20.5 万元
负责人:
周婧容
学科分类:
H1814.肿瘤化学药物治疗
结题年份:
2022
批准年份:
2019
项目状态:
已结题
项目参与者:
--
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中文摘要
恶性胶质瘤的有效治疗是生物医学领域的关键性问题。加之,纳米药物如何最有效地穿透血管到达肿瘤部位的问题尚待解决。本项目前期发现纳米药物Basolite F-300@GOD(金属有机骨架材料Basolite F-300与葡萄糖氧化酶GOD的复合纳米药物)递送系统能在肿瘤微环境低pH响应的情况下凋亡血管内皮细胞,从而既有利于改善肿瘤微血管通透性又能抗血管生成。结合前期实验进展,提出了通过饥饿治疗和ROS(活性氧)协同治疗,纳米药物Basolite F-300@GOD@anti-VEGFR2(anti-VEGFR2用于靶向肿瘤微血管内皮细胞)既能凋亡血管内皮细胞,又能凋亡肿瘤的假说。拟用胶质瘤细胞和血管内皮细胞的体外毒性实验和小鼠体内治疗实验结合的方法进行胶质瘤抗血管生成和肿瘤治疗研究,探索凋亡血管内皮细胞与纳米药物递送效率的关系,以改善肿瘤微血管通透性,增强纳米药物治疗效果。
英文摘要
The effective treatment of glioblastoma is a key problem in the field of biomedicine. Moreover, the question of how nano-drug can effectively penetrate blood vessels to reach the tumor site remains to be solved. In the early stage of this project, it was found that the delivery system of nano-drug Basolite F-300@GOD (nanoscaled composite materials of Metal Organic Frameworks Basolite F-300 and Glucose Oxidase) could cause the apoptosis of vascular endothelial cells under the condition of low pH response in the tumor microenvironment, which leads to improving the tumor microvascular permeability and anti-angiogenesis. Combined with the previous experimental progress, a hypothesis was proposed that the nano-drug Basolite F-300@GOD@anti-VEGFR2 (anti-VEGFR2 was used for targeting tumor microvascular endothelial cells ) could both cause the apoptosis of vascular endothelial cells and glioma cells through the synergistic effect of starvation therapy and ROS (Reactive Oxygen Species) therapy. It is proposed to study the anti-angiogenesis and tumor apoptosis of glioma by combining in vitro toxicity experiment and in vivo treatment experiment, and to explore the relationship between the apoptosis of vascular endothelial cells and delivery efficiency of nano-drugs. The aim is to improve the tumor microvascular permeability and enhance the therapeutic effect of nano-drugs.
研究利用靶向血管的金属有机框架(MOFs)纳米药物(MGaV NPs),结合级联催化增强CDT和anti-VEGFR2诱导的抗血管生成治疗,解决纳米药物如何有效地穿透血管到达肿瘤部位的问题以提高癌症治疗疗效。选择Fe-MOF (Basolite F-300)作为葡萄糖氧化酶GOD负载基质,随后进行anti-VEGFR2表面功能化。在智能级联催化纳米药物 (MGaV NPs)中,GOD可以催化葡萄糖分解触发肿瘤饥饿,并提供H2O2作为底物,用于Fe-MOF催化类芬顿反应生成对肿瘤CDT剧毒的•OH。而anti-VEGFR2诱导纳米平台靶向肿瘤微血管,阻断VEGF-VEGFR2连接以抗血管生成。体外和体内实验结果表明,智能纳米药物MGaV NPs可以诱导肿瘤细胞和肿瘤周围血管内皮细胞的凋亡。本研究提示,MGaV NPs能有效的靶向血管治疗肿瘤,通过破坏现有的血管系统,阻止肿瘤组织中新的血管生成。这种智能癌症治疗策略,结合了级联催化增强CDT和 anti-VEGFR2诱导的抗血管生成治疗,具有很好的肿瘤和肿瘤微血管治疗疗效。
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Anti-VEGFR2-labeled Enzyme-Immobilized Metal-Organic Frameworks for Tumor Vasculature Targeted Catalytic Therapy
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
发表时间:2022
期刊:Acta Biomaterialia
影响因子:9.7
作者:Jingrong Zhou;Kai Wang;Shuaishuai Ding;Lijuan Zeng;Jingya Miao;Yuhua Cao;Xiao Zhang;Gan Tian;Biu-wu Bian
通讯作者:Biu-wu Bian
DOI:https://doi.org/10.1016/j.actbio.2022.01.037
发表时间:2022
期刊:Acta Biomaterialia
影响因子:9.7
作者:Jingrong Zhou;Kai Wang;Shuaishuai Ding;Lijuan Zeng;Jingya Miao;Yuhua Cao;Xiao Zhang;Gan Tian;Biu-wu Bian
通讯作者:Biu-wu Bian
国内基金
海外基金