Cancer cell membrane-coated biomimetic platform for tumor targeted photodynamic therapy and hypoxia-amplified bioreductive therapy
Cancer cell membrane-coated biomimetic platform for tumor targeted photodynamic therapy and hypoxia-amplified bioreductive therapy
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用于肿瘤靶向光动力治疗和缺氧放大生物还原治疗的癌细胞膜涂层仿生平台
DOI：
10.1016/j.biomaterials.2017.07.026
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发表时间：
2017-10-01
期刊：
影响因子：
14
通讯作者：
Zhang, Xian-Zheng
中科院分区：
文献类型：
--
作者：
Li, Shi-Ying;Cheng, Hong;Zhang, Xian-Zheng
调节肿瘤微环境以提高治疗效率将是一种有效的癌症治疗新策略。在这项工作中，基于负载替拉扎明（TPZ）的卟啉金属有机框架PCN - 224（PCN代表多孔配位网络），构建了一种癌细胞膜包覆的纳米平台（TPZ@PCN@Mem），用于肿瘤靶向光动力疗法（PDT）以及随后产生的缺氧放大的生物还原疗法。给药后，由于癌细胞膜包覆赋予的免疫逃逸和同源靶向性，TPZ@PCN@Mem在肿瘤组织中表现出选择性积累和长期滞留。在光照下，PCN - 224介导产生有毒的活性氧物质（ROS）用于光动力疗法，由此产生的局部缺氧微环境将进一步加速TPZ的激活，从而增强对4T1原位肿瘤的化疗效果。TPZ@PCN@Mem的级联协同治疗效果可显著抑制原发肿瘤的生长，并以最小的副作用抑制其远端转移。该研究表明，利用这种仿生策略进行肿瘤靶向光动力疗法和缺氧激活的生物还原疗法具有极大的优势，为精确有效的肿瘤治疗提供了新的思路。（C）2017爱思唯尔有限公司。保留所有权利。
Modulating tumor microenvironment to amplify the therapeutic efficiency would be a novel strategy for effective cancer treatment. In this work, based on the TPZ-loaded porphyrinic metal organic framework PCN-224 (PCN stands for porous coordination network), a cancer cell membrane-coated nanoplatform (TPZ@PCN@Mem) was fabricated for tumor targeted PDT and the successively resulting hypoxia-amplified bioreductive therapy. After administration, TPZ@PCN@Mem exhibited the selective accumulation and long-term retention at tumor tissue due to the immune escape and homologous targeting endowed by the cancer membrane coating. Upon light irradiation, PCN-224-mediated toxic reactive oxygen species (ROS) were generated for PDT, and the resulting local hypoxia microenvironment would further accelerate the activation of TPZ for enhanced chemotherapy in 4T1 orthotopic tumor. The cascade synergistic therapeutic effects of TPZ@PCN@Mem could significantly suppress the primary tumor growth, and also inhibit its distal metastasis with minimal side effects. The study indicated an overwhelming superiority of utilizing this bioinspired strategy for tumor targeted PDT and hypoxia-activated bioreductive therapy, which provided a new insight for precise and effective tumor treatment. (C) 2017 Elsevier Ltd. All rights reserved.