title: A polyphenylene dendrimer drug transporter with precisely positioned amphiphilic surface patches.
abstract: The design and synthesis of a polyphenylene dendrimer (PPD 3) with discrete binding sites for lipophilic guest molecules and characteristic surface patterns is presented. Its semi-rigidity in combination with a precise positioning of hydrophilic and hydrophobic groups at the periphery yields a refined architecture with lipophilic binding pockets that accommodate defined numbers of biologically relevant guest molecules such as fatty acids or the drug doxorubicin. The size, architecture, and surface textures allow to even penetrate brain endothelial cells that are a major component of the extremely tight blood-brain barrier. In addition, low to no toxicity is observed in in vivo studies using zebrafish embryos. The unique PPD scaffold allows the precise placement of functional groups in a given environment and offers a universal platform for designing drug transporters that closely mimic many features of proteins.
authors.affiliation: Max Planck Institute for Polymer Research, Ackermannweg 10, 55128, Mainz, Germany.
authors.forename: René
authors.initials: R
authors.lastname: Stangenberg
authors.forename: Yuzhou
authors.initials: Y
authors.lastname: Wu
authors.forename: Jana
authors.initials: J
authors.lastname: Hedrich
authors.forename: Dennis
authors.initials: D
authors.lastname: Kurzbach
authors.forename: Daniel
authors.initials: D
authors.lastname: Wehner
authors.forename: Gilbert
authors.initials: G
authors.lastname: Weidinger
authors.forename: Seah Ling
authors.initials: SL
authors.lastname: Kuan
authors.forename: Malin Insa
authors.initials: MI
authors.lastname: Jansen
authors.forename: Fedor
authors.initials: F
authors.lastname: Jelezko
authors.forename: Heiko J
authors.initials: HJ
authors.lastname: Luhmann
authors.forename: Dariush
authors.initials: D
authors.lastname: Hinderberger
authors.forename: Tanja
authors.initials: T
authors.lastname: Weil
authors.forename: Klaus
authors.initials: K
authors.lastname: Müllen
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology; D002460:Cell Line / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D050091:Dendrimers / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers; D015195:Drug Design; D004625:Embryo, Nonmammalian / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution; D015027:Zebrafish / Q000196:embryology
chemical_list: D050091:Dendrimers; D004337:Drug Carriers; D011108:Polymers; D004317:Doxorubicin; C041325:polyphenylene sulfide
keywords: amphiphilic surface patches; drug transporters; polyphenylene dendrimers; protein-like functions