Multifunctional Programmable DNA Nanotrain for Activatable Hypoxia Imaging and Mitochondrion-Targeted Enhanced Photodynamic Therapy.
Multifunctional Programmable DNA Nanotrain for Activatable Hypoxia Imaging and Mitochondrion-Targeted Enhanced Photodynamic Therapy.
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DOI：
10.1021/acsami.0c21681
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发表时间：
2021-02
影响因子：
9.5
通讯作者：
Jin Liu;Ge Ding;Shiya Chen;Caoye Xue;Mian Chen;Xueqin Wu;Quan Yuan;Jing Zheng;Ronghua Yang
中科院分区：
文献类型：
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作者：
Jin Liu;Ge Ding;Shiya Chen;Caoye Xue;Mian Chen;Xueqin Wu;Quan Yuan;Jing Zheng;Ronghua Yang
可编程的基于DNA的纳米结构（例如，纳米列车、纳米花和DNA树枝状聚合物）为安全有效的生物成像和肿瘤治疗提供了新的方法。然而，很少有研究报道，基于DNA的纳米结构响应缺氧微环境的可激活成像和细胞器靶向肿瘤治疗。在此，我们创新性地报道了一种偶氮还原酶响应性的、靶向靶向多功能可编程DNA纳米列车，用于可激活的缺氧成像和增强光动力学治疗（PDT）的功效。花青结构染料（Cy 3）和黑洞淬灭剂2（BHQ 2），其分别用作荧光靶向分子和偶氮还原酶响应元件，共价连接到DNA发夹单体。在DNA发夹单体末端的延伸的富含鸟嘌呤（G）的序列充当光敏剂5，10，15，20-四（4-N-甲基吡啶鎓基）卟啉（TMPyP 4）的纳米载体。在DNA发夹单体和引发探针之间引发后，BHQ 2通过荧光共振能量转移（FRET）过程有效地猝灭了可编程纳米链中Cy 3的荧光和TMPyP 4的单线态氧（1 O2）生成。一旦可编程纳米列车进入癌细胞，BHQ 2中的偶氮键将在缺氧条件下通过偶氮还原酶的高表达还原为氨基;然后，Cy 3的荧光和TMPyP 4的1 O2生成将显著恢复。此外，由于Cy 3赋予的靶向肿瘤细胞的特性，负载TMPyP 4的纳米列车将在癌细胞的线粒体中积累，然后在光照射下表现出增强的PDT功效。我们期望这种基于可编程DNA纳米列车的多功能纳米平台可以有效地用于缺氧相关生物医学领域的可激活成像和高性能PDT。
Programmable DNA-based nanostructures (e.g., nanotrains, nanoflowers, and DNA dendrimers) provide new approaches for safe and effective biological imaging and tumor therapy. However, few studies have reported that DNA-based nanostructures respond to the hypoxic microenvironment for activatable imaging and organelle-targeted tumor therapy. Herein, we innovatively report an azoreductase-responsive, mitochondrion-targeted multifunctional programmable DNA nanotrain for activatable hypoxia imaging and enhanced efficacy of photodynamic therapy (PDT). Cyanine structural dye (Cy3) and black hole quencher 2 (BHQ2), which were employed as a fluorescent mitochondrion-targeted molecule and azoreductase-responsive element, respectively, covalently attached to the DNA hairpin monomers. The extended guanine (G)-rich sequence at the end of the DNA hairpin monomer served as a nanocarrier for the photosensitizer 5,10,15,20-tetrakis(4-N-methylpyridiniumyl) porphyrin (TMPyP4). Upon initiation between the DNA hairpin monomer and initiation probe, the fluorescence of Cy3 and the singlet oxygen (1O2) generation of TMPyP4 in the programmable nanotrain were effectively quenched by BHQ2 through the fluorescence resonance energy transfer (FRET) process. Once the programmable nanotrain entered cancer cells, the azo bond in BHQ2 will be reduced to amino groups by the high expression of azoreductase under hypoxia conditions; then, the fluorescence of Cy3 and the 1O2 generation of TMPyP4 will significantly be restored. Furthermore, due to the mitochondrion-targeting characteristic endowed by Cy3, the TMPyP4-loaded nanotrain would accumulate in the mitochondria of cancer cells and then demonstrate enhanced PDT efficacy under light irradiation. We expect that this programmable DNA nanotrain-based multifunctional nanoplatform could be effectively used for activatable imaging and high performance of PDT in hypoxia-related biomedical field.