title: Polyvalent saccharide-functionalized generation 3 poly(amidoamine) dendrimer-methotrexate conjugate as a potential anticancer agent.
abstract: A saccharide-terminated generation 3 (G3) polyamidoamine (PAMAM) dendrimer was synthesized as a drug carrier. Utilizing this dendritic platform, we have successfully synthesized polyvalent conjugates (G3-MTX) containing the drug methotrexate (MTX). Surface Plasmon Resonance (SPR) results showed that G3-MTX presented three orders of magnitude enhancement in binding avidity to folate-binding protein (FBP) as compared to the free folic acid (FA). Flow cytometric and confocal microscopic analysis showed that conjugate (G3-MTX-FI) containing imaging agent fluorescein-5(6)-carboxamidohexanoic acid (FI) was internalized into folate receptor (FR)-expressing KB cells in dose-dependent and receptor-mediated fashion. The G3-MTX induced a dose-dependent cytotoxicity in the KB cells. Therefore, the polyvalent G3-MTX may have potential as an anticancer nanodevice for the specific targeting and killing of FR-expressing tumor cells.
authors: Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan, Ann Arbor, MI 48109, USA.
authors: Yuehua
authors: Y
authors: Zhang
authors: Thommey P
authors: TP
authors: Thomas
authors: Kyung-Hoon
authors: KH
authors: Lee
authors: Minghsin
authors: M
authors: Li
authors: Hong
authors: H
authors: Zong
authors: Ankur M
authors: AM
authors: Desai
authors: Alina
authors: A
authors: Kotlyar
authors: Baohua
authors: B
authors: Huang
authors: Mark M Banaszak
authors: MM
authors: Holl
authors: James R
authors: JR
authors: Baker
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D002241:Carbohydrates; D045744:Cell Line, Tumor; D050091:Dendrimers / Q000737:chemistry* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D058975:Folate Receptor 1; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage*; D011073:Polyamines; D011485:Protein Binding / Q000187:drug effects
chemical_list: D000964:Antimetabolites, Antineoplastic; D002241:Carbohydrates; D050091:Dendrimers; D004337:Drug Carriers; C548696:FOLR1 protein, human; D058975:Folate Receptor 1; D011073:Polyamines; D008727:Methotrexate