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Vehiculization determines the endocytic internalization mechanism of Zn(II)-phthalocyanine.
MedLine Citation:
PMID:  22899479     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
It is generally accepted that compounds of nanomolecular size penetrate into cells by different endocytic processes. The vehiculization strategy of a compound is a factor that could determine its uptake mechanism. Understanding the influence of the vehicle in the precise mechanism of drug penetration into cells makes possible to improve or modify the therapeutic effects. In this study, using human A-549 cells, we have characterized the possible internalization mechanism of the photosensitizer Zn(II)-phthalocyanine (ZnPc), either dissolved in dimethylformamide (ZnPc-DMF) or included in liposomes of dipalmitoyl-phosphatidyl-choline. Specific inhibitors involved in the main endocytic pathways were used. Co-incubation of cells with ZnPc-liposomes and dynasore (dinamin-mediated endocytosis inhibitor) resulted in a significant decrease of photodamage, whereas other inhibitors did not alter the photodynamic effect of ZnPc. On the contrary, cells treated with ZnPc-DMF in the presence of dynasore, genistein (caveolin-mediated endocytosis inhibitor) or cytochalasin D (macropinocytosis and caveolin-mediated endocytosis inhibitor) showed a significant decrease in ZnPc uptake and photodynamic damage. These results suggest that ZnPc-DMF penetrates into cells mainly by caveolin-mediated endocytosis, whereas ZnPc-liposomes are internalized into cells preferentially by clathrin-mediated endocytosis. We conclude that using different drug vehiculization systems, it is possible to modify the internalization mechanism of a therapeutic compound, which could be of great interest in clinical research.
Authors:
Jorge Soriano; Angeles Villanueva; Juan C Stockert; Magdalena Cañete
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-17
Journal Detail:
Title:  Histochemistry and cell biology     Volume:  -     ISSN:  1432-119X     ISO Abbreviation:  Histochem. Cell Biol.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9506663     Medline TA:  Histochem Cell Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Departamento de Biología, Facultad de Ciencias, Universidad Autónoma de Madrid, 28049, Madrid, Spain.
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