G-Quadruplex-Based Nanoscale Coordination Polymers to Modulate Tumor Hypoxia and Achieve Nuclear-Targeted Drug Delivery for Enhanced Photodynamic Therapy.
G-Quadruplex-Based Nanoscale Coordination Polymers to Modulate Tumor Hypoxia and Achieve Nuclear-Targeted Drug Delivery for Enhanced Photodynamic Therapy.
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DOI：
10.1021/acs.nanolett.8b02732
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发表时间：
2018-10
期刊：
影响因子：
10.8
通讯作者：
Yu Yang;Wenjun Zhu;Liangzhu Feng;Y. Chao;Xuan Yi;Z. Dong;Kai Yang;W. Tan;Zhuang Liu;
中科院分区：
文献类型：
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作者：
Yu Yang;Wenjun Zhu;Liangzhu Feng;Y. Chao;Xuan Yi;Z. Dong;Kai Yang;W. Tan;Zhuang Liu;
光动力疗法（PDT）是一种光触发疗法，用于通过产生活性氧（ROS）来杀死癌细胞。本文通过一种简单的方法，将钙离子（Ca 2+）与AS 1411 DNA G四链体配位形成纳米配位聚合物（NCPs），制备了一种新型的DNA纳米结构。氯e6（Ce 6），光敏剂，和氯化血红素，含铁的卟啉，可以插入到G-四链体结构中获得的NCP。通过进一步的聚乙二醇（PEG）修饰，我们获得了Ca-AS 1411/Ce 6/hemin@pHis-PEG（CACH-PEG）NCP纳米结构，其使得光敏剂Ce 6能够在核内转运，从而在最易受ROS影响的细胞核内产生ROS。同时，通过AS 1411抑制抗凋亡蛋白B细胞淋巴瘤2（Bcl-2）的表达，可以大大改善PDT诱导的细胞凋亡。此外，G-quadruplexes和hemin的过氧化氢酶模拟DNAzyme功能可以分解肿瘤内源性H2 O2，原位产生氧气，从而通过克服缺氧相关的阻力进一步增强PDT。这项工作开发了一种简单而通用的方法来制造基于DNA的NCP，并提出了一个有趣的概念，纳米级药物递送系统，可以实现光敏剂的核内递送，抗凋亡蛋白的下调，以及同时改善癌症治疗的不利肿瘤微环境的调制。
Photodynamic therapy (PDT) is a light-triggered therapy used to kill cancer cells by producing reactive oxygen species (ROS). Herein, a new kind of DNA nanostructure based on the coordination between calcium ions (Ca2+) and AS1411 DNA G quadruplexes to form nanoscale coordination polymers (NCPs) is developed via a simple method. Both chlorine e6 (Ce6), a photosensitizer, and hemin, an iron-containing porphyrin, can be inserted into the G-quadruplex structure in the obtained NCPs. With further polyethylene glycol (PEG) modification, we obtain Ca-AS1411/Ce6/hemin@pHis-PEG (CACH-PEG) NCP nanostructure that enables the intranuclear transport of photosensitizer Ce6 to generate ROS inside cell nuclei that are the most vulnerable to ROS. Meanwhile, the inhibition of antiapoptotic protein B-cell lymphoma 2 (Bcl-2) expression by AS1411 allows for greatly improved PDT-induced cell apoptosis. Furthermore, the catalase-mimicking DNAzyme function of G-quadruplexes and hemin in those NCPs could decompose tumor endogenous H2O2 to in situ generate oxygen so as to further enhance PDT by overcoming the hypoxia-associated resistance. This work develops a simple yet general method with which to fabricate DNA-based NCPs and presents an interesting concept of a nanoscale drug-delivery system that could achieve the intranuclear delivery of photosensitizers, the down-regulation of anti-apoptotic proteins, and the modulation of the unfavorable tumor microenvironment simultaneously for improved cancer therapy.