Increased uptake of liposomal–dna complexes by lung metastases following intravenous administration
We have investigated the effects of an improved liposomal formulation (extruded DOTAP:cholesterol (DOTAP:Chol)–DNA complex) on transgene expression in tumor cells and normal cells of murine and human origin both in vitro and in vivo. In vitro, transgene expression was significantly increased (P = 0....
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| Veröffentlicht in: | Molecular therapy 2003-03, Vol.7 (3), p.409-418 |
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| creator | Ito, Isao Began, Gopalan Mohiuddin, Imran Saeki, Tomoyuki Saito, Yuji Branch, Cynthia D Vaporciyan, Ara Clifton Stephens, L Yen, Nancy Roth, Jack A Ramesh, Rajagopal |
| description | We have investigated the effects of an improved liposomal formulation (extruded DOTAP:cholesterol (DOTAP:Chol)–DNA complex) on transgene expression in tumor cells and normal cells of murine and human origin both in vitro and in vivo. In vitro, transgene expression was significantly increased (P = 0.01) in human tumor cells compared to normal human cells. The increased transgene expression was due to increased uptake of the liposome–DNA complex by tumor cell phagocytosis. Furthermore, immunohistochemical analysis demonstrated a greater transgene expression in lung tumors than in surrounding normal tissues. Increased transgene expression due to enhanced uptake of the liposome–DNA complexes by tumor cells in vivo was also demonstrated using fluorescently labeled DOTAP:Chol liposomes. Finally, evaluation of lung tissue explants obtained from patients undergoing pulmonary resection demonstrated significantly higher (P = 0.001) transgene expression in tumor cells than in normal cells. Thus, we demonstrated that intravenous injection of DOTAP:Chol–DNA complex results in increased transgene expression in tumor and is due to increased phagocytosis of the complexes by tumor cells. |
| doi_str_mv | 10.1016/S1525-0016(03)00004-2 |
| format | Article |
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In vitro, transgene expression was significantly increased (P = 0.01) in human tumor cells compared to normal human cells. The increased transgene expression was due to increased uptake of the liposome–DNA complex by tumor cell phagocytosis. Furthermore, immunohistochemical analysis demonstrated a greater transgene expression in lung tumors than in surrounding normal tissues. Increased transgene expression due to enhanced uptake of the liposome–DNA complexes by tumor cells in vivo was also demonstrated using fluorescently labeled DOTAP:Chol liposomes. Finally, evaluation of lung tissue explants obtained from patients undergoing pulmonary resection demonstrated significantly higher (P = 0.001) transgene expression in tumor cells than in normal cells. Thus, we demonstrated that intravenous injection of DOTAP:Chol–DNA complex results in increased transgene expression in tumor and is due to increased phagocytosis of the complexes by tumor cells.</description><identifier>ISSN: 1525-0016</identifier><identifier>EISSN: 1525-0024</identifier><identifier>DOI: 10.1016/S1525-0016(03)00004-2</identifier><identifier>PMID: 12668137</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; cancer ; Cancer therapies ; Carcinoma, Non-Small-Cell Lung - metabolism ; Carcinoma, Non-Small-Cell Lung - secondary ; Carcinoma, Non-Small-Cell Lung - therapy ; Cell Survival ; Cholesterol - metabolism ; DNA - metabolism ; Fatty Acids, Monounsaturated - metabolism ; Gene expression ; Gene therapy ; Genetic Therapy ; Heart surgery ; Humans ; Immunoenzyme Techniques ; Injections, Intravenous ; liposome ; Liposomes ; Luciferases - metabolism ; Lung Neoplasms - metabolism ; Lung Neoplasms - secondary ; Lung Neoplasms - therapy ; Lungs ; Metastasis ; Mice ; Mice, Inbred C3H ; Microscopy ; Phagocytosis ; Pinocytosis ; Protein expression ; Proteins ; Quaternary Ammonium Compounds - metabolism ; Toxicity ; Transgenes ; Tumor Cells, Cultured ; Tumors</subject><ispartof>Molecular therapy, 2003-03, Vol.7 (3), p.409-418</ispartof><rights>2003 The American Society of Gene Therapy</rights><rights>Copyright Nature Publishing Group Mar 2003</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c502t-20e53cd0c38dc7002a331cb9c8c422b9e69469a8a8f78cc02dee02149c6617c73</citedby><cites>FETCH-LOGICAL-c502t-20e53cd0c38dc7002a331cb9c8c422b9e69469a8a8f78cc02dee02149c6617c73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12668137$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ito, Isao</creatorcontrib><creatorcontrib>Began, Gopalan</creatorcontrib><creatorcontrib>Mohiuddin, Imran</creatorcontrib><creatorcontrib>Saeki, Tomoyuki</creatorcontrib><creatorcontrib>Saito, Yuji</creatorcontrib><creatorcontrib>Branch, Cynthia D</creatorcontrib><creatorcontrib>Vaporciyan, Ara</creatorcontrib><creatorcontrib>Clifton Stephens, L</creatorcontrib><creatorcontrib>Yen, Nancy</creatorcontrib><creatorcontrib>Roth, Jack A</creatorcontrib><creatorcontrib>Ramesh, Rajagopal</creatorcontrib><title>Increased uptake of liposomal–dna complexes by lung metastases following intravenous administration</title><title>Molecular therapy</title><addtitle>Mol Ther</addtitle><description>We have investigated the effects of an improved liposomal formulation (extruded DOTAP:cholesterol (DOTAP:Chol)–DNA complex) on transgene expression in tumor cells and normal cells of murine and human origin both in vitro and in vivo. In vitro, transgene expression was significantly increased (P = 0.01) in human tumor cells compared to normal human cells. The increased transgene expression was due to increased uptake of the liposome–DNA complex by tumor cell phagocytosis. Furthermore, immunohistochemical analysis demonstrated a greater transgene expression in lung tumors than in surrounding normal tissues. Increased transgene expression due to enhanced uptake of the liposome–DNA complexes by tumor cells in vivo was also demonstrated using fluorescently labeled DOTAP:Chol liposomes. Finally, evaluation of lung tissue explants obtained from patients undergoing pulmonary resection demonstrated significantly higher (P = 0.001) transgene expression in tumor cells than in normal cells. Thus, we demonstrated that intravenous injection of DOTAP:Chol–DNA complex results in increased transgene expression in tumor and is due to increased phagocytosis of the complexes by tumor cells.</description><subject>Animals</subject><subject>cancer</subject><subject>Cancer therapies</subject><subject>Carcinoma, Non-Small-Cell Lung - metabolism</subject><subject>Carcinoma, Non-Small-Cell Lung - secondary</subject><subject>Carcinoma, Non-Small-Cell Lung - therapy</subject><subject>Cell Survival</subject><subject>Cholesterol - metabolism</subject><subject>DNA - metabolism</subject><subject>Fatty Acids, Monounsaturated - metabolism</subject><subject>Gene expression</subject><subject>Gene therapy</subject><subject>Genetic Therapy</subject><subject>Heart surgery</subject><subject>Humans</subject><subject>Immunoenzyme Techniques</subject><subject>Injections, Intravenous</subject><subject>liposome</subject><subject>Liposomes</subject><subject>Luciferases - metabolism</subject><subject>Lung Neoplasms - 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Academic</collection><jtitle>Molecular therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ito, Isao</au><au>Began, Gopalan</au><au>Mohiuddin, Imran</au><au>Saeki, Tomoyuki</au><au>Saito, Yuji</au><au>Branch, Cynthia D</au><au>Vaporciyan, Ara</au><au>Clifton Stephens, L</au><au>Yen, Nancy</au><au>Roth, Jack A</au><au>Ramesh, Rajagopal</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increased uptake of liposomal–dna complexes by lung metastases following intravenous administration</atitle><jtitle>Molecular therapy</jtitle><addtitle>Mol Ther</addtitle><date>2003-03</date><risdate>2003</risdate><volume>7</volume><issue>3</issue><spage>409</spage><epage>418</epage><pages>409-418</pages><issn>1525-0016</issn><eissn>1525-0024</eissn><abstract>We have investigated the effects of an improved liposomal formulation (extruded DOTAP:cholesterol (DOTAP:Chol)–DNA complex) on transgene expression in tumor cells and normal cells of murine and human origin both in vitro and in vivo. In vitro, transgene expression was significantly increased (P = 0.01) in human tumor cells compared to normal human cells. The increased transgene expression was due to increased uptake of the liposome–DNA complex by tumor cell phagocytosis. Furthermore, immunohistochemical analysis demonstrated a greater transgene expression in lung tumors than in surrounding normal tissues. Increased transgene expression due to enhanced uptake of the liposome–DNA complexes by tumor cells in vivo was also demonstrated using fluorescently labeled DOTAP:Chol liposomes. Finally, evaluation of lung tissue explants obtained from patients undergoing pulmonary resection demonstrated significantly higher (P = 0.001) transgene expression in tumor cells than in normal cells. 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| ispartof | Molecular therapy, 2003-03, Vol.7 (3), p.409-418 |
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| subjects | Animals cancer Cancer therapies Carcinoma, Non-Small-Cell Lung - metabolism Carcinoma, Non-Small-Cell Lung - secondary Carcinoma, Non-Small-Cell Lung - therapy Cell Survival Cholesterol - metabolism DNA - metabolism Fatty Acids, Monounsaturated - metabolism Gene expression Gene therapy Genetic Therapy Heart surgery Humans Immunoenzyme Techniques Injections, Intravenous liposome Liposomes Luciferases - metabolism Lung Neoplasms - metabolism Lung Neoplasms - secondary Lung Neoplasms - therapy Lungs Metastasis Mice Mice, Inbred C3H Microscopy Phagocytosis Pinocytosis Protein expression Proteins Quaternary Ammonium Compounds - metabolism Toxicity Transgenes Tumor Cells, Cultured Tumors |
| title | Increased uptake of liposomal–dna complexes by lung metastases following intravenous administration |
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