Alteration of the glycosylation pattern of monocytic THP-1 cells upon differentiation and its impact on lectin-mediated drug delivery.
In the present study, human monocytic THP-1 cells were treated with phorbol-12-myristate-13-acetate (PMA) in order to obtain macrophage-like cells. Before and after treatment, plant lectins with distinct sugar specificities were applied in order to elucidate the glycosylation patterns of both monocytic and macrophage-like cell types and to follow changes during differentiation. As a result of flow-cytometric analyses, for untreated as well as for PMA-differentiated cells WGA yielded the highest binding rate without significant changes in the binding capacity. For the other lectins, divergent results were obtained which point to reorganization of sugar residues on the cell surface during differentiation. Additionally, cytoinvasion being beneficial for enhanced drug absorption was studied with WGA which had displayed a high binding capacity together with a high specificity. For both untreated and PMA-differentiated cells decreased fluorescence intensity at 37 degrees C as compared to 4 degrees C was observable pointing to internalization and accumulation within acidic compartments. Moreover, WGA-functionalized PLGA nanoparticles were prepared, and their uptake evaluated. Uptake rates of 55% in case of PMA-differentiated cells suggested that WGA-grafted drug delivery systems might be an interesting approach for treatment of infectious diseases provoked by parasites, facultative intracellular bacteria, or viruses such as HIV.
Plattner
V E
VE
Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Vienna, Austria.
Ratzinger
G
G
Engleder
E T
ET
Gallauner
S
S
Gabor
F
F
Wirth
M
M
D050260:Carbohydrate Metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D005434:Flow Cytometry; D006031:Glycosylation; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D008264:Macrophages / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D053758:Nanoparticles; D037121:Plant Lectins / Q000378:metabolism*; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013696:Temperature; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology; D014909:Wheat Germ Agglutinins / Q000378:metabolism*
D004337:Drug Carriers; D037121:Plant Lectins; D014909:Wheat Germ Agglutinins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C016658:phorbolol myristate acetate; D013755:Tetradecanoylphorbol Acetate