Chen Qiaoshu, Li Chunying, Yang Xiaohai, Huang Jin, Liu Songyang, Liu Wei, Liu Jianbo, Wang Kemin
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha 410082, P. R. China.
J Mater Chem B. 2017 Sep 28;5(36):7529-7537. doi: 10.1039/c7tb01590a. Epub 2017 Aug 31.
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.
为了将鸡尾酒化疗和光动力疗法整合到一种生物相容性和可生物降解的纳米载体中，制备了自组装DNA纳米线，并将其与光敏剂二氢卟吩e6（Ce6）和化疗药物阿霉素（DOX）共同负载，用于抗肿瘤化学光动力联合治疗。两条短DNA链作为构建模块，通过超三明治杂交反应自组装形成DNA纳米线，成功形成了500个碱基的线性DNA纳米线，长度相当于167纳米。Ce6和DOX分别通过共价或非共价嵌入相互作用负载到纳米线上。DNA纳米线被细胞摄取，释放的Ce6和DOX最终分布在不同的细胞区室中。与游离Ce6相比，负载光敏剂的纳米线显示出光动力活性氧（ROS）的生成增加。与单独的化疗或光动力疗法相比，负载双药的DNA纳米线提供的联合治疗显著增加了HepG-2细胞死亡的发生率，并在癌细胞治疗中产生了明显的协同效应。DNA纳米线纳米载体提供了一个灵活且定量的载药模块，可对两种药物进行剂量控制。更重要的是，DNA纳米线在抗肿瘤化学光动力联合治疗中显示出强大的协同效应，这可能是由于光动力ROS生成增加以及Ce6和DOX在不同细胞内区室中的分布。这项工作表明，DNA纳米线可能作为癌症治疗中化学光动力模式的多功能有效治疗纳米载体。
