Endothelial cell transfection with cationic liposomes and herpes simplex-thymidine kinase mediated killing.
Endothelial cells are a promising target for cancer gene therapy because neoangiogenesis is vital for the supply of oxygen and nutrients to solid tumours. However, endothelial cells have been reported to be difficult to transfect. We demonstrate high rates of transfection with the reporter gene pSV40 beta gal using DC-Chol/DOPE cationic liposomes and lower rates with the novel polyamine cationic liposomes ACHx/DC-Chol/DOPE and ACO/DC-Chol/DOPE. Endothelial cells transfected with HSV-thymidine kinase using DC-Chol/DOPE demonstrated 3 log10 increased cytotoxicity compared with controls when exposed to the prodrug ganciclovir, thereby demonstrating significant biological effect.
Fife
K
K
Departmet of Medical Oncology, Charing Cross and Westminster Medical School, London, UK.
Bower
M
M
Cooper
R G
RG
Stewart
L
L
Etheridge
C J
CJ
Coombes
R C
RC
Buluwela
L
L
Miller
A D
AD
D002412:Cations; D002460:Cell Line; D004337:Drug Carriers; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015774:Ganciclovir / Q000008:administration & dosage*; D017930:Genes, Reporter; D005814:Genes, Viral; D005822:Genetic Vectors; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008081:Liposomes / Q000008:administration & dosage*; D011073:Polyamines; D013539:Simian virus 40 / Q000235:genetics; D018139:Simplexvirus / Q000201:enzymology / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics*; D014162:Transfection / Q000379:methods*; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D002412:Cations; D004337:Drug Carriers; D008055:Lipids; D008081:Liposomes; D011073:Polyamines; D013937:Thymidine Kinase; D001616:beta-Galactosidase; D015774:Ganciclovir