Selective gene transfer to endometrial cancer cells by a polymer against matrix metalloproteinase 2 (MMP-2).
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.
Han
Joo Youn
JY
Department of Biological Sciences, Ajou University, Suwon, South Korea.
Choi
Dong Soon
DS
Kim
Changhoon
C
Joo
Hyun
H
Min
Churl K
CK
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
D000906:Antibodies; D007097:Imines; D011095:Polyethylenes; C505405:poly(ethylene imine); D004247:DNA; D020778:Matrix Metalloproteinase 2