The aim of this study was to compare the potential of two
plant lectins [
peanut agglutinin (PNA) and
wheat germ agglutinin (WGA)],
monoclonal antibody (anti-Thy-1.2), its F(ab')(2) fragments, and
galactosamine as targeting moieties bound to the
polymer drug carrier to deliver a
xenobiotic,
doxorubicin, to selected
cancer cell lines. We have used primary (SW 480, HT 29) and metastatic (SW 620) human
colorectal cancer cell lines and a transfectant, genetically engineered SW 620 cell line with mouse gene Thy-1.2 (SW 620/T) to test the possibility of marking human
cancer with xenogeneic mouse gene and use it for effective site-specific targeting. The targeting moieties and
doxorubicin were conjugated to a water-soluble copolymer based on
N-(2-hydroxypropyl)methacrylamide (
HPMA) acting as a carrier responsible for controlled intracellular release of the targeted drug. FACS analysis showed a strong binding of WGA-
FITC to all tested cell lines. Binding of PNA-
FITC was considerably weaker. The in vitro antiproliferative effect of
lectin-targeted
HPMA carrier-bound
doxorubicin evaluated as [(3)H]TdR incorporation reflected both the intensity of the binding and the different sensitivity of the tested
cancer cells lines to
doxorubicin. The antiproliferative effect of conjugates targeted with WGA was comparable to that with the conjugates targeted with the anti-Thy-1.2
monoclonal antibody or their F(ab')(2) fragments. The magnitude of the cytotoxic effect of
HPMA-
doxorubicin targeted with PNA was lower in all tested cell lines. While the conjugates with WGA were more cytotoxic, the conjugates with PNA were more specific as their binding is limited to
cancer cells and to the sites of
inflammation. Noncytotoxic conjugates with a very low concentration of
doxorubicin and targeted with PNA, anti-Thy-1.2, or their F(ab')(2) fragments exerted in some lines (SW 480, SW 620) low mitogenic activity. The Thy-1.2 gene-transfected SW 620 metastatic
colorectal cancer cell line was sensitive to the antiproliferative effect of Thy-1.2-targeted
doxorubicin as was shown for the Thy-1. 2(+) EL4 cell line and for Thy-1.2(+)
concanavalin A-stimulated mouse T lymphocytes. These results represent the first indication of the suitability of transfection of human
cancer cells with selected targeting genes for site-specific
therapy of
malignancies.