TY - JOUR
T1 - The role of galactose, lactose, and galactose valency in the biorecognition of N-(2-hydroxypropyl)methacrylamide copolymers by human colon adenocarcinoma cells
AU - David, Ayelet
AU - Kopecková, Pavla
AU - Kopeček, Jindrich
AU - Rubinstein, Abraham
N1 - Funding Information:
This work was supported in part by research grants from the BSF (98-00449), from the Israel Cancer Association (20000026-B), and from the National Institutes of Health (DK39544). We thank Mr. K. Jensen (University of Utah) and Dr. S. Haupt and Ms. A. Brestovitsky (The Hebrew University) for assistance with the confocal microscopy analysis.
PY - 2002/1/1
Y1 - 2002/1/1
N2 - Purpose. To examine the β-galactoside and β-lactoside binding capacity of three human colon-adenocarcinoma cell lines and their sugar specificity, using N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer conjugates of galactosamine, lactose, and triantennary galactose. Methods. Three types of HPMA copolymers containing the saccharide epitopes galactosamine (P-Gal), lactose (P-Lac), or triantennary galactose (P-TriGal) were synthesized. The relationship between the content of the saccharide moieties, the valency of the galactose residues, and their biorecognition by the cell lines (Colo-205, SW-480, and SW-620) was investigated using flow cytometry and confocal fluorescence microscopy analysis. Results. The binding of the glycoconjugates to the human colon-adenocarcinoma cell lines was dependent on the type and the number of bound sugar residues per macromolecule. The higher the sugar contents in the HPMA copolymers, the higher the extent of binding. Although introduction of galactoside residues into the HPMA copolymer resulted in a significant increase in the binding of the co-polymers to the cells, low biorecognition of the lactoside-containing HPMA copolymers by all cell lines used was observed. The trivalent galactoside-containing HPMA copolymers did not yield a notable glycoside cluster effect for the β-galactoside-binding lectin expressed on human colon-adenocarcinoma cells. Among the various cell lines, little differences in the extent of binding of the glycopolymers to the cells were observed. The data on the internalization of HPMA co-polymer conjugates obtained by confocal fluorescence microscopy correlated well with the flow cytometry analysis of their biorecognition by target cells. Conclusions. The lectin-mediated endocytosis of the HPMA-glycoconjugates in human colon cancer cell lines suggests their potential use as targeting tools of cytotoxic drugs to colon adenocarcinoma.
AB - Purpose. To examine the β-galactoside and β-lactoside binding capacity of three human colon-adenocarcinoma cell lines and their sugar specificity, using N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer conjugates of galactosamine, lactose, and triantennary galactose. Methods. Three types of HPMA copolymers containing the saccharide epitopes galactosamine (P-Gal), lactose (P-Lac), or triantennary galactose (P-TriGal) were synthesized. The relationship between the content of the saccharide moieties, the valency of the galactose residues, and their biorecognition by the cell lines (Colo-205, SW-480, and SW-620) was investigated using flow cytometry and confocal fluorescence microscopy analysis. Results. The binding of the glycoconjugates to the human colon-adenocarcinoma cell lines was dependent on the type and the number of bound sugar residues per macromolecule. The higher the sugar contents in the HPMA copolymers, the higher the extent of binding. Although introduction of galactoside residues into the HPMA copolymer resulted in a significant increase in the binding of the co-polymers to the cells, low biorecognition of the lactoside-containing HPMA copolymers by all cell lines used was observed. The trivalent galactoside-containing HPMA copolymers did not yield a notable glycoside cluster effect for the β-galactoside-binding lectin expressed on human colon-adenocarcinoma cells. Among the various cell lines, little differences in the extent of binding of the glycopolymers to the cells were observed. The data on the internalization of HPMA co-polymer conjugates obtained by confocal fluorescence microscopy correlated well with the flow cytometry analysis of their biorecognition by target cells. Conclusions. The lectin-mediated endocytosis of the HPMA-glycoconjugates in human colon cancer cell lines suggests their potential use as targeting tools of cytotoxic drugs to colon adenocarcinoma.
KW - Biorecognition
KW - Colon-adenocarcinoma cells
KW - Confocal microscopy
KW - Galectin
KW - HPMA copolymer
KW - Lectin-mediated drug targeting
UR - http://www.scopus.com/inward/record.url?scp=0036690721&partnerID=8YFLogxK
U2 - 10.1023/A:1019885807067
DO - 10.1023/A:1019885807067
M3 - Article
AN - SCOPUS:0036690721
SN - 0724-8741
VL - 19
SP - 1114
EP - 1122
JO - Pharmaceutical Research
JF - Pharmaceutical Research
IS - 8
ER -
