ZFIN ID: ZDB-PUB-140904-10
A Polyphenylene Dendrimer Drug Transporter with Precisely Positioned Amphiphilic Surface Patches
Stangenberg, R., Wu, Y., Hedrich, J., Kurzbach, D., Wehner, D., Weidinger, G., Kuan, S.L., Jansen, M.I., Jelezko, F., Luhmann, H.J., Hinderberger, D., Weil, T., Müllen, K.
Date: 2015
Source: Advanced Healthcare Materials   4(3): 377-84 (Journal)
Registered Authors: Wehner, Daniel, Weidinger, Gilbert
Keywords: amphiphilic surface patches, drug transporters, polyphenylene dendrimers, protein-like functions
MeSH Terms:
  • Animals
  • Brain/cytology
  • Cell Line/drug effects
  • Chemistry Techniques, Synthetic
  • Dendrimers/administration & dosage*
  • Dendrimers/chemistry*
  • Dendrimers/pharmacokinetics
  • Doxorubicin/administration & dosage*
  • Doxorubicin/chemistry
  • Drug Carriers
  • Drug Design
  • Embryo, Nonmammalian/drug effects
  • Endothelial Cells/drug effects
  • Endothelial Cells/metabolism
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Mice
  • Polymers/administration & dosage*
  • Polymers/chemistry
  • Polymers/pharmacokinetics
  • Tissue Distribution
  • Zebrafish/embryology
PubMed: 25182694 Full text @ Adv. Healthc. Mater.
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.