Self-assembled DNA nanowires as quantitative dual-drug nanocarriers for antitumor chemophotodynamic combination therapy,Journal of Materials Chemistry B

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Self-assembled DNA nanowires as quantitative dual-drug nanocarriers for antitumor chemophotodynamic combination therapy
Journal of Materials Chemistry B ( IF 6.1 ) Pub Date : 2017-08-14 00:00:00 , DOI: 10.1039/c7tb01590a
Qiaoshu Chen _{1,

2,

3,

4,

5} , Chunying Li _{1,

2,

3,

4,

5} , Xiaohai Yang _{1,

2,

3,

4,

5} , Jin Huang _{1,

2,

3,

4,

5} , Songyang Liu _{1,

2,

3,

4,

5} , Wei Liu _{1,

2,

3,

4,

5} , Jianbo Liu _{1,

2,

3,

4,

5} , Kemin Wang _{1,

2,

3,

4,

5}

Affiliation

To combine cocktail chemotherapy and photodynamic therapy into one biocompatible and biodegradable nanocarrier, self-assembled DNA nanowires were fabricated and co-loaded with a photosensitizer chlorin e6 (Ce6) and a chemotherapeutic drug doxorubicin (DOX) for antitumor chemophotodynamic combination therapy. Two short DNA chains served as building blocks for the self-assembly of DNA nanowires in a supersandwich hybridization reaction that led to the successful formation of linear DNA nanowires of 500 bases, equal to a length of 167 nm. Ce6 and DOX were loaded onto the nanowires through covalent or noncovalent intercalation interactions, respectively. The DNA nanowires were taken up into cells, and the released Ce6 and DOX were ultimately distributed in different cellular compartments. The photosensitizer-loaded nanowires demonstrated increased generation of photodynamic reactive oxygen species (ROS) compared to that of free Ce6. In comparison with chemo- or photodynamic therapy alone, the combined treatment provided by DNA nanowires loaded with dual-drug significantly increased the incidence of HepG-2 cell death and produced a clear synergistic effect in the treatment of cancer cells. The DNA nanowire nanocarrier provided a flexible and quantitative drug-loading module that allowed for dose control of both drugs. More importantly, the DNA nanowires demonstrate a strong synergistic effect in antitumor chemophotodynamic combination therapy, likely because of increased photodynamic ROS generation and the distribution of Ce6 and DOX in different intracellular compartments. This work suggests that DNA nanowires may be useful as multifunctional and effective therapeutic nanocarriers for chemophotodynamic modalities in cancer therapy.

中文翻译：

自组装DNA纳米线作为抗肿瘤化学光动力学联合疗法的定量双药纳米载体

为了将鸡尾酒疗法和光动力疗法结合到一种生物相容且可生物降解的纳米载体中，制造了自组装的DNA纳米线，并与光敏性二氢卟酚e6（Ce6）和化学治疗药物阿霉素（DOX）共同装载，用于抗肿瘤化学光动力联合疗法。在超三明治杂交反应中，两条短的DNA链充当了DNA纳米线自组装的基础，从而成功形成了500个碱基（等于167 nm）的线性DNA纳米线。Ce6和DOX分别通过共价或非共价插层相互作用加载到纳米线上。DNA纳米线被吸收到细胞中，释放的Ce6和DOX最终分布在不同的细胞区室中。与游离的Ce6相比，负载光敏剂的纳米线显示出增加的光动力学活性氧（ROS）生成。与单独的化学疗法或光动力疗法相比，DNA纳米线负载双药的联合治疗显着增加了HepG-2细胞死亡的发生率，并在治疗癌细胞中产生了明显的协同作用。DNA纳米线纳米载体提供了灵活且定量的载药模块，可控制两种药物的剂量。更重要的是，DNA纳米线在抗肿瘤化学光动力联合疗法中显示出强大的协同作用，这可能是由于光动力ROS生成增加以及Ce6和DOX在不同细胞内区室的分布增加所致。

更新日期：2017-09-20

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