Poly-(amidoamine) dendrimers with a precisely core positioned sulforhodamine B molecule for comparative biological tracing and profiling

Lin Ping Wu, Mario Ficker, Søren L. Mejlsøe, Arnaldur Hall, Valentina Paolucci, Jørn B. Christensen, Panagiotis N. Trohopoulos, Seyed Moghimi

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

We report on a simple robust procedure for synthesis of generation-4 poly-(amidoamine) (PAMAM) dendrimers with a precisely core positioned single sulforhodamine B molecule. The labelled dendrimers exhibited high fluorescent quantum yields where the absorbance and fluorescence spectrum of the fluorophore was not affected by pH and temperature. Since the stoichiometry of the fluorophore to the dendrimer is 1:1, we were able to directly compare uptake kinetics, the mode of uptake, trafficking and safety of dendrimers of different end-terminal functionality (carboxylated vs. pyrrolidonated) by two phenotypically different human endothelial cell types (the human brain capillary endothelial cell line hCMEC/D3 and human umbilical vein endothelial cells), and without interference of the fluorophore in uptake processes. The results demonstrate comparable uptake kinetics and a predominantly clathrin-mediated endocytotic mechanism, irrespective of dendrimer end-terminal functionality, where the majority of dendrimers are directed to the endo-lysosomal compartments in both cell types. A minor fraction of dendrimers, however, localize to endoplasmic reticulum and the Golgi apparatus, presumably through the recycling endosomes. In contrast to amino-terminated PAMAM dendrimers, we confirm safety of carboxylic acid- and pyrrolidone-terminated PAMAM dendrimers through determination of cell membrane integrity and comprehensive respiratory profiling (measurements of mitochondrial oxidative phosphorylation and determination of its coupling efficiency). Our dendrimer core-labelling approach could provide a new conceptual basis for improved understanding of dendrimer performance within biological settings.

Original languageEnglish (US)
Pages (from-to)88-97
Number of pages10
JournalJournal of Controlled Release
Volume246
DOIs
StatePublished - Jan 28 2017

Keywords

  • Cytotoxicity
  • Dendrimers
  • Endothelial cells
  • Fluorescent probes
  • Nanomaterials

ASJC Scopus subject areas

  • Pharmaceutical Science

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