Intracellular uptake and intracavitary targeting of folate-conjugated liposomes in a mouse lymphoma model with up-regulated folate receptors.

作者: Hilary Shmeeda , Lidia Mak , Dina Tzemach , Peleg Astrahan , Mark Tarshish

DOI: 10.1158/1535-7163.MCT-05-0543

关键词: Cell sortingIn vivoChemistryFluoresceinPharmacologyLiposomeCancer researchTargeted drug deliveryLigand (biochemistry)Folate receptorFluorescence microscope

摘要: The folate receptor is overexpressed in a broad spectrum of malignant tumors and represents an attractive target for selective delivery anticancer agents to receptor–expressing tumors. This study examines folate-lipid conjugates as means enhancing the tumor selectivity liposome-encapsulated drugs mouse lymphoma model. Folate-derivatized polyethylene glycol (PEG3350)-distearoyl-phosphatidylethanolamine was post-loaded at various concentrations into following preparations: radiolabeled PEGylated liposomes, liposomes labeled aqueous compartment with dextran fluorescein, liposomal doxorubicin (PLD, Doxil). We incubated folate-targeted or fluorescent J6456 cells up-regulated their receptors (J6456-FR) determine optimal ligand concentration required lipid bilayer cell association, examine whether are internalized by J6456-FR suspension. Liposomal association quantified based on radioactivity fluorescence-activated sorting analysis, internalization assessed confocal fluorescence microscopy. found molar ∼0.5% using our ligand. A substantial dose-dependent increase cell-associated compared nontargeted liposomes. Confocal depth scanning showed that amount cells. Binding uptake PLD were also observed vivo after i.p. injection mice bearing ascitic drug levels increased 17-fold, whereas those plasma decreased 14-fold when Folate-targeted represent approach intracellular seem be promising tool intracavitary targeting. [Mol Cancer Ther 2006;5(4):818–24]

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