title: Selective gene transfer to endometrial cancer cells by a polymer against matrix metalloproteinase 2 (MMP-2).
abstract: A novel cancer-cell-specific gene delivery vector with high transfection efficiency was designed and tested with an in vitro coculture consisting of the human endometrial adenocarcinoma cell line, HEC-1A cells, and normal endometrial stromal cells. For the cancer-cell targeting, polyethylenimine (PEI), a cationic polymer that can be easily combined with anionic DNA to form a particulate complex, polyplex, being capable of transferring a gene into a variety of cells, was covalently conjugated with antibodies against matrix metalloproteinase 2 (MMP-2), a typical surface-marker protein on cancer cells known for its close correlation with angiogenesis and invasion in many types of cancer, using the heterofunctional cross-linker, n-succinimidyl 3-(2-pyridyldithio)-propionamide. Biophysical properties and transfection efficiencies of anti-MMP-2-conjugated PEI were analyzed by means of dynamic light scattering, laser Doppler anemometry, and flow cytometry. Our results reveal that (1) the PEI-anti-MMP-2 antibody conjugate maintains physical parameters, including sizes and surface charges, which appear to be favorable for gene transfer and (2) when the pEGFP-N3 plasmid complexes of the PEI-anti-MMP-2 antibody conjugate are applied to the coculture consisting of HEC-1A cells and human stromal cells, a high level of green fluorescent protein expression occurs in HEC-1A cells over stromal cells, suggesting a specific gene transfer targeting cancer cells. Therefore, targeting invading cancer cells with the PEI-anti-MMP-2 antibody conjugate could be promising in endometrial cancer treatment, and this gene delivery system deserves further optimization in the context of targeted therapeutic gene delivery.
authors.affiliation: Department of Biological Sciences, Ajou University, Suwon, South Korea.
authors.forename: Joo Youn
authors.initials: JY
authors.lastname: Han
authors.forename: Dong Soon
authors.initials: DS
authors.lastname: Choi
authors.forename: Changhoon
authors.initials: C
authors.lastname: Kim
authors.forename: Hyun
authors.initials: H
authors.lastname: Joo
authors.forename: Churl K
authors.initials: CK
authors.lastname: Min
mesh_terms: D000906:Antibodies / Q000737:chemistry / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000235:genetics; D016889:Endometrial Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007097:Imines / Q000737:chemistry* / Q000633:toxicity; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015394:Molecular Structure; D011095:Polyethylenes / Q000737:chemistry* / Q000633:toxicity; D019076:Transgenes / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D000906:Antibodies; D007097:Imines; D011095:Polyethylenes; C505405:poly(ethylene imine); D004247:DNA; D020778:Matrix Metalloproteinase 2