DNA Polyplexes as Combinatory Drug Carriers of Doxorubicin and Cisplatin: An in Vitro Study

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• 作者：Han Chang Kang ; Hana Cho ; You Han Bae
• 刊名：Molecular Pharmaceutics
• 出版年：2015
• 出版时间：August 3, 2015
• 年：2015
• 卷：12
• 期：8
• 页码：2845-2857
• 全文大小：899K
• ISSN：1543-8392

文摘

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鈥?70 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- to 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 鈥渃arrier DNA鈥?to the 鈥渘uclear DNA鈥?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.