title: Design, synthesis, and biological functionality of a dendrimer-based modular drug delivery platform.
abstract: A modular dendrimer-based drug delivery platform was designed to improve upon existing limitations in single dendrimer systems. Using this modular strategy, a biologically active platform containing receptor mediated targeting and fluorescence imaging modules was synthesized by coupling a folic acid (FA) conjugated dendrimer with a fluorescein isothiocyanate (FITC) conjugated dendrimer. The two different dendrimer modules were coupled via the 1,3-dipolar cycloaddition reaction ("click" chemistry) between an alkyne moiety on the surface of the first dendrimer and an azide moiety on the second dendrimer. Two simplified model systems were also synthesized to develop appropriate "click" reaction conditions and aid in spectroscopic assignments. Conjugates were characterized by (1)H NMR spectroscopy and NOESY. The FA-FITC modular platform was evaluated in vitro with a human epithelial cancer cell line (KB) and found to specifically target the overexpressed folic acid receptor.
authors.affiliation: Programs in Macromolecular Science and Engineering, University of Michigan , Ann Arbor, Michigan 48019, United States.
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Mullen
authors.forename: Daniel Q
authors.initials: DQ
authors.lastname: McNerny
authors.forename: Ankur
authors.initials: A
authors.lastname: Desai
authors.forename: Xue-Min
authors.initials: XM
authors.lastname: Cheng
authors.forename: Stassi C
authors.initials: SC
authors.lastname: Dimaggio
authors.forename: Alina
authors.initials: A
authors.lastname: Kotlyar
authors.forename: Yueyang
authors.initials: Y
authors.lastname: Zhong
authors.forename: Suyang
authors.initials: S
authors.lastname: Qin
authors.forename: Christopher V
authors.initials: CV
authors.lastname: Kelly
authors.forename: Thommey P
authors.initials: TP
authors.lastname: Thomas
authors.forename: Istvan
authors.initials: I
authors.lastname: Majoros
authors.forename: Bradford G
authors.initials: BG
authors.lastname: Orr
authors.forename: James R
authors.initials: JR
authors.lastname: Baker
authors.forename: Mark M
authors.initials: MM
authors.lastname: Banaszak Holl
mesh_terms: D057930:Click Chemistry; D050091:Dendrimers / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D016503:Drug Delivery Systems; D015195:Drug Design; D005456:Fluorescent Dyes / Q000737:chemistry; D058973:Folate Receptors, GPI-Anchored / Q000032:analysis* / Q000096:biosynthesis; D005492:Folic Acid / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D017879:Isothiocyanates / Q000737:chemistry; D007624:KB Cells; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D013499:Surface Properties; D014407:Tumor Cells, Cultured
chemical_list: D050091:Dendrimers; D004337:Drug Carriers; D005456:Fluorescent Dyes; D058973:Folate Receptors, GPI-Anchored; D017879:Isothiocyanates; C037152:isothiocyanic acid; D005492:Folic Acid