title: Delivery of calf thymus DNA to tumor by folate receptor targeted cationic liposomes.
abstract: Calf thymus DNA (ctDNA) has been shown to stimulate macrophages to produce cytokines both in vitro and in vivo when complexed with cationic liposomes. In addition, direct cytotoxicity of ctDNA has been found in tissue culture and in mice. In this study, ctDNA and folate receptor targeted cationic liposome complexes (ctDNA-F-CLs) were prepared and evaluated in FR (+) tumors. In addition, the underlying mechanism for the anti-cancer activity of ctDNA-F-CLs was investigated. Selective uptake of ctDNA-F-CLs was observed in FR (+) KB and L1210JF cells using flow cytometry. In RAW264.7 cells and DBA/2 mice, ctDNA-F-CLs and ctDNA-N-CLs significantly induced TNF-α and IL-6 production compared to free ctDNA. However, no significant difference in cytokine production was observed between ctDNA-N-CLs and ctDNA-F-CLs. In tumor bearing DBA/2 mice, ctDNA-F-CLs significantly increased INF-γ and IL-6 production compared to ctDNA-N-CLs. Furthermore in L1210JF cells, ctDNA-F-CLs had significantly increased cytotoxicity compared to ctDNA-N-CLs. Tumor cell apoptosis was also found in co-culture of RAW264.7 cells and ctDNA-F-CLs treated L1210JF cells. In L1210JF tumor bearing mice, ctDNA-F-CLs were found to significantly inhibit tumor growth and prolong the median survival time (MeST). In contrast, ctDNA-N-CLs and free ctDNA showed similar activities for tumor inhibition and animal survival. Moreover, the anti-cancer effect of ctDNA-F-CL was further enhanced by combination with anti-cancer drug doxorubicin. These results suggest that ctDNA-F-CLs are a promising agent for treatment of FR-positive tumors.
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Longzhu
authors.initials: L
authors.lastname: Piao
authors.affiliation: Department of Chemical, Biomolecular Engineering, The Ohio State University, Columbus, OH 43210, USA.|NSF Nanoscale Science and Engineering Center (NSEC), The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Yu
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Bryant C
authors.initials: BC
authors.lastname: Yung
authors.affiliation: Department of Biochemistry and Chemistry, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Wenpeng
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Chemistry, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Peng G
authors.initials: PG
authors.lastname: Wang
authors.affiliation: Department of Chemical, Biomolecular Engineering, The Ohio State University, Columbus, OH 43210, USA.|NSF Nanoscale Science and Engineering Center (NSEC), The Ohio State University, Columbus, OH 43210, USA.
authors.forename: James L
authors.initials: JL
authors.lastname: Lee
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.|NSF Nanoscale Science and Engineering Center (NSEC), The Ohio State University, Columbus, OH 43210, USA.|Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002412:Cations; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D004247:DNA / Q000378:metabolism* / Q000633:toxicity; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use; D016503:Drug Delivery Systems / Q000379:methods*; D004359:Drug Therapy, Combination; D058973:Folate Receptors, GPI-Anchored / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000473:pathology; D008081:Liposomes / Q000737:chemistry* / Q000633:toxicity; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D002412:Cations; D016207:Cytokines; D058973:Folate Receptors, GPI-Anchored; D008081:Liposomes; D049452:Green Fluorescent Proteins; D004317:Doxorubicin; D004247:DNA; C427203:calf thymus DNA