title: Enhancement of gene expression by transcriptional activation using doxorubicin-loaded liposome/pDNA complexes.
abstract: Gene therapy is a promising treatment option for cancers generated by mutation of oncogenes or tumor suppressor genes. The transcriptional process is activated by doxorubicin (DXR), and gene expression efficiency followed by gene transfection can be enhanced by the combination-use of DXR. Therefore, co-encapsulation of plasmid DNA (pDNA) and DXR into non-viral gene carriers can enhance gene expression. Here, we prepared DXR-loaded liposome/pDNA complexes (DXR-loaded PEGylated lipoplexes) by co-encapsulating pDNA and DXR into liposomes. Gene expression was enhanced by DXR encapsulation into lipoplexes in colon-26 cells and cultured mouse macrophages, and this gene expression level was significantly higher than that obtained by the combination of PEGylated lipoplexes and free DXR. Moreover, the activation profiles of transcriptional factors induced by DXR-loaded lipoplexes were different from those induced by free DXR; therefore, co-encapsulation of pDNA and DXR into gene carriers might be contributed to effective enhancement of gene expression. These findings provide a new approach for achieving effective gene transfection using PEGylated lipoplexes.
authors: Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
authors: K
authors: K
authors: Un
authors: Y
authors: Y
authors: Kono
authors: M
authors: M
authors: Yoshida
authors: F
authors: F
authors: Yamashita
authors: S
authors: S
authors: Kawakami
authors: M
authors: M
authors: Hashida
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000494:pharmacology*; D002460:Cell Line; D004396:Coloring Agents; D004247:DNA / Q000008:administration & dosage* / Q000096:biosynthesis / Q000235:genetics*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000494:pharmacology*; D004337:Drug Carriers; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D008081:Liposomes; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000235:genetics; D010316:Particle Size; D011092:Polyethylene Glycols; D060888:Real-Time Polymerase Chain Reaction; D013778:Tetrazolium Salts; D013844:Thiazoles; D018808:Transcription Factor AP-1 / Q000235:genetics; D015533:Transcriptional Activation / Q000187:drug effects*
chemical_list: D000903:Antibiotics, Antineoplastic; D004396:Coloring Agents; D004337:Drug Carriers; D008081:Liposomes; D016328:NF-kappa B; D013778:Tetrazolium Salts; D013844:Thiazoles; D018808:Transcription Factor AP-1; D011092:Polyethylene Glycols; D004317:Doxorubicin; D004247:DNA; C022616:thiazolyl blue