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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2002-1-9
pubmed:abstractText
The intracellular uptake and localization of a fluorescently labeled Pluronic P-105 in HL-60 leukemia cells and in A2780 drug-sensitive and A2780/ADR MDR ovarian carcinoma cells were characterized by flow cytometry and fluorescence microscopy. Pluronic P-105 molecules were labeled with a pH-sensitive fluorescent label, 5-(and 6-)carboxy-2'7'-dichlorofluorescein. The fluorescence intensity of labeled Pluronic was about twofold higher at pH 7.4 than at pH 5.5. At Pluronic concentrations exceeding the critical micelle concentration (cmc), flow cytometry histograms manifested bimodal distribution of cell fluorescence for all types of cells. Cell population characterized by higher fluorescence intensity presumably resulted from Pluronic transfer from the acidic environment of cytoplasmic vesicles (endosomes or lysosomes) into the neutral environment of the cytoplasm and cell nuclei, which suggested the permeabilization of the membranes of acidic vesicle by Pluronic molecules. For the MDR cells, the bimodal distribution of cell fluorescence was already observed at very low Pluronic concentrations in the incubation medium (i.e., below the cmc). The data suggest that the membranes of acidic vesicles of MDR cells are more susceptible to the action of polymeric surfactants than those of drug-sensitive cells. Permeabilization of acidic vesicles had a dramatic effect on the intracellular trafficking of drugs: when delivered in PBS, the anthracyclin drug ruboxyl (Rb) sequestered in cytoplasmic vesicles and was excluded from cell nuclei; however, when delivered in Pluronic micelles, drug accumulated in cell nuclei. Drug uptake from/with Pluronic micelles was substantially enhanced by ultrasound. These findings suggest that the nuclear accumulation of drugs internalized via fluid-phase endocytosis can be enhanced by the application of Pluronic micelles and can be further augmented by ultrasonic irradiation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-3549
pubmed:author
pubmed:copyrightInfo
Copyright 2002 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:volume
91
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
157-70
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Intracellular uptake and trafficking of Pluronic micelles in drug-sensitive and MDR cells: effect on the intracellular drug localization.
pubmed:affiliation
Department of Bioengineering, University of Utah, 20 S. 2030 E., Room 108, Salt Lake City, Utah, USA. natasha.rapoport@m.cc.utah.edu
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.