Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan 430072, PR China.
Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan 430072, PR China; The Institute for Advanced Studies, Wuhan University, Wuhan 430072, PR China.
Biomaterials. 2017 Oct;142:149-161. doi: 10.1016/j.biomaterials.2017.07.026. Epub 2017 Jul 18.
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.
调节肿瘤微环境以增强治疗效果将是一种有效的癌症治疗的新策略。在这项工作中,基于负载 TPZ 的卟啉金属有机骨架 PCN-224(PCN 代表多孔配位网络),制备了一种癌细胞膜包覆的纳米平台(TPZ@PCN@Mem),用于肿瘤靶向 PDT 以及随后产生的缺氧增强的生物还原治疗。给药后,由于癌症膜涂层赋予的免疫逃逸和同源靶向作用,TPZ@PCN@Mem 表现出选择性聚集和在肿瘤组织中的长期保留。在光照射下,PCN-224 介导的毒性活性氧(ROS)被用于 PDT,并且由此产生的局部缺氧微环境将进一步加速 TPZ 的激活,以增强 4T1 原位肿瘤的化学治疗。TPZ@PCN@Mem 的级联协同治疗效果可显著抑制原发性肿瘤的生长,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 PDT 和缺氧激活的生物还原治疗具有压倒性的优势,为精确有效的肿瘤治疗提供了新的思路。
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