Targeted drug delivery: binding and uptake of plant lectins using human 5637 bladder cancer cells.
In an effort to detect novel strategies in bladder cancer therapy, the potential and the applicability of different plant lectins was investigated using 5637 cells as a model for human urinary carcinoma. The cell-lectin interaction studies were performed with single cells as well as monolayers using flow cytometry and fluorimetry. As a result, wheat germ agglutinin (WGA) and Ulex europaeus agglutinin (UEA) revealed strongest interaction with single cells demonstrating a high presence of N-acetyl-d-glucosamine, sialic acid and alpha-l-fucose residues on the membrane surface. Considering monolayers, binding of most lectins depended on the culturing period pointing to a change in the glycocalyx composition during cultivation. However, constant binding capacities combined with a high specificity were detected for WGA. Cytoinvasion studies were performed with WGA and revealed a decreased fluorescence intensity at 37 degrees C as compared to 4 degrees C, which points to internalisation of the lectin and accumulation in acidic compartments. Intracellular localization was confirmed by addition of monensin that compensates the pH-gradient between acidic compartments and cytoplasm leading to a full reversal of the decline in fluorescence. According to these findings, some lectins, especially WGA, offer promising features for targeting drugs to bladder cancer cells. This might be interesting for the development of functionalized drug delivery systems for site specific antitumor therapy leading to reduced toxicity, prolonged exposition, and improved efficacy.
Plattner
Verena E
VE
Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Vienna, Austria.
Wagner
Maria
M
Ratzinger
Gerda
G
Gabor
Franz
F
Wirth
Michael
M
D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D005434:Flow Cytometry; D005470:Fluorometry; D006801:Humans; D037121:Plant Lectins / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014909:Wheat Germ Agglutinins / Q000378:metabolism
D037121:Plant Lectins; D014909:Wheat Germ Agglutinins