Targeting and Inhibition of Cell Growth by an Engineered Dendritic Nanodevice
| Autor: | Anna U. Bielinska, James R. Baker, Thommey P. Thomas, Alina Kotlyar, Istvan J. Majoros, Jolanta F. Kukowska-Latallo, and Andrzej Myc |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
musculoskeletal diseases
Antineoplastic Agents KB Cells chemistry.chemical_compound Drug Delivery Systems Folic Acid Dendrimer Drug Discovery Polyamines Humans skin and connective tissue diseases Cytotoxicity Cell Proliferation Fluorescent Dyes Drug Carriers Cell growth In vitro Nanostructures Methotrexate chemistry Biochemistry Cell culture Biophysics Molecular Medicine Growth inhibition Drug carrier Fluorescein-5-isothiocyanate Conjugate |
| Zdroj: | Journal of Medicinal Chemistry. 48:3729-3735 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | The cellular uptake and cytotoxicity of an engineered multifunctional dendritic nanodevice containing folic acid (FA) as the targeting molecule, methotrexate (MTX) as the chemotherapeutic drug, and fluorescein (FI) as the detecting agent were studied in vitro. FI and FA were conjugated to the generation 5 poly(amidoamine) (G5) dendrimer carrier through a thiourea and amide linkage and MTX was conjugated through an ester linkage to the carrier to generate the trifunctional dendritic device, G5-FI-FA-MTX. This trifunctional dendrimer-drug conjugate bound to FA receptor-expressing KB cells in a dose-dependent and saturable manner. Confocal microscopic analysis demonstrated cellular internalization of the conjugate. G5-FI-FA-MTX induced a time- and dose-dependent inhibition of cell growth in KB cells. The targeted dendrimer conjugates G5-FI-FA-MTX and G5-FA-MTX inhibited cell growth in KB cells, whereas the nontargeted G5-MTX failed to induce growth inhibition. These studies show the potential of G5-FI-FA-MTX or G5-FA-MTX for targeting and growth suppression of tumor cells that overexpress FA-receptors. |
| Databáze: | OpenAIRE |
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