title: DNA Polyplexes as Combinatory Drug Carriers of Doxorubicin and Cisplatin: An in Vitro Study.
abstract: 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- 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 "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.
authors.affiliation: †Department of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, College of Pharmacy, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do 420-743, Republic of Korea.
authors.forename: Han Chang
authors.initials: HC
authors.lastname: Kang
authors.affiliation: †Department of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, College of Pharmacy, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do 420-743, Republic of Korea.
authors.forename: Hana
authors.initials: H
authors.lastname: Cho
authors.affiliation: ‡Department of Pharmaceutics and Pharmaceutical Chemistry, The University of Utah, 30 S 2000 E, Rm 2972, Salt Lake City, Utah 84112, United States.|§Utah-Inha Drug Delivery Systems (DDS) and Advanced Therapeutics Research Center, 7-50 Songdo-dong, Yeonsu-gu, Incheon 406-840, Republic of Korea.
authors.forename: You Han
authors.initials: YH
authors.lastname: Bae
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry*; D004317:Doxorubicin / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D018014:Gene Transfer Techniques; D006801:Humans; D066298:In Vitro Techniques; D008156:Luciferases / Q000378:metabolism; D061986:MCF-7 Cells; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000473:pathology; D010957:Plasmids / Q000008:administration & dosage; D011108:Polymers / Q000737:chemistry*; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D004337:Drug Carriers; D011108:Polymers; D004317:Doxorubicin; D004247:DNA; D008156:Luciferases; D002945:Cisplatin
keywords: DNA binding; DNA intercalation; combination therapy; nanocarrier; pDNA; polyplex