title: Targeting and inhibition of cell growth by an engineered dendritic nanodevice.
abstract: 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.
authors.affiliation: Center for Biologic Nanotechnology, University of Michigan Medical School, 9220 MSRB III, Ann Arbor, Michigan 48109-0648, USA. thommey@umich.edu
authors.forename: Thommey P
authors.initials: TP
authors.lastname: Thomas
authors.forename: Istvan J
authors.initials: IJ
authors.lastname: Majoros
authors.forename: Alina
authors.initials: A
authors.lastname: Kotlyar
authors.forename: Jolanta F
authors.initials: JF
authors.lastname: Kukowska-Latallo
authors.forename: Anna
authors.initials: A
authors.lastname: Bielinska
authors.forename: Andrzej
authors.initials: A
authors.lastname: Myc
authors.forename: James R
authors.initials: JR
authors.lastname: Baker
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D004337:Drug Carriers; D016503:Drug Delivery Systems; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D005492:Folic Acid / Q000737:chemistry*; D006801:Humans; D007624:KB Cells; D008727:Methotrexate / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D049329:Nanostructures; D011073:Polyamines / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D005456:Fluorescent Dyes; D011073:Polyamines; D005492:Folic Acid; D016650:Fluorescein-5-isothiocyanate; D008727:Methotrexate