DNA Polyplexes as Combinatory Drug Carriers of Doxorubicin and Cisplatin: An in Vitro Study.
DNA Polyplexes as Combinatory Drug Carriers of Doxorubicin and Cisplatin: An in Vitro Study.
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DOI：
10.1021/mp500873k
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发表时间：
2015-08-03
影响因子：
4.9
通讯作者：
Bae YH
中科院分区：
文献类型：
--
作者：
Kang HC;Cho H;Bae YH
双螺旋核酸用作阿霉素（DOX）和顺铂（CDDP）的组合药物载体，阿霉素（DOX）与DNA双螺旋物理嵌入，顺铂（CDDP）与DNA结合而不发生烷基化反应。与DOX、CDDP或两者相互作用的DNA与带正电荷的内体溶解聚合物复合。与游离药物相比，聚合物（100 ~ 170 nm）将更多的药物递送到细胞质和细胞核中，并表现出相似或上级的体外细胞杀伤活性（最多增加7倍）。此外，大多数化学药物负载质粒DNA（pDNA）复合物的基因表达活性不受核酸与DOX/CDDP之间的物理相互作用的损害。当使用模型报告基因pDNA（荧光素酶）时，其表达的荧光素酶蛋白的量是由没有结合药物的多聚物（对照）表达的量的0.7- 1.4倍，这表明嵌入或结合的药物从“载体DNA”快速移位到靶细胞的“核DNA”。所提出的概念可能提供遗传物质和小分子药物的多功能组合疗法的可能性，所述小分子药物与核酸结合以治疗各种疾病。
Double helix nucleic acids were used as a combination drug carrier for doxorubicin (DOX), which physically intercalates with DNA double helices, and cisplatin (CDDP), which binds to DNA without an alkylation reaction. DNA interacting with DOX, CDDP, or both was complexed with positively charged, endosomolytic polymers. Compared with the free drug, the polyplexes (100 ~ 170 nm in size) delivered more drug into the cytosol and the nucleus and demonstrated similar or superior (up to a 7-fold increase) in vitro cell-killing activity. Additionally, the gene expression activities of most of the chemical drug-loaded plasmid DNA (pDNA) polyplexes were not impaired by the physical interactions between the nucleic acid and DOX/CDDP. When a model reporter pDNA (luciferase) was employed, it expressed luciferase protein at 0.7- ~ 1.4-fold the amount expressed by the polyplex with no bound drugs (a control), which indicated the fast translocation of the intercalated or bound drugs from the “carrier DNA” to the “nuclear DNA” of target cells. The proposed concept may offer the possibility of versatile combination therapies of genetic materials and small molecule drugs that bind to nucleic acids to treat various diseases.