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Polyglycerol-based amphiphilic dendrons as potential siRNA carriers for in vivo applications

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Published copy (DOI)


  • A. Tschiche
  • A.M. Staedtler
  • S. Malhotra
  • H. Bauer
  • C. Böttcher
  • S. Sharbati
  • M. Calderón
  • M. Koch
  • T.M. Zollner
  • A. Barnard
  • D.K. Smith
  • R. Einspanier
  • N. Schmidt
  • R. Haag


Publication details

JournalJournal of Materials Chemistry B
DatePublished - 7 Mar 2014
Issue number15
Number of pages15
Pages (from-to)2153-2167
Original languageEnglish


The development of nonviral synthetic vectors for clinical application of gene therapy using siRNA transfection technology is of particular importance for treatment of human diseases, which is yet an unsolved challenge. By employing a rational design approach, we have synthesized a set of well-defined, low-molecular-weight dendritic polyglycerol-based amphiphiles, which are decorated peripherally with the DAPMA (N,N-di-(3-aminopropyl)-N-(methyl)amine) moiety. The main differences that were introduced in the structural motif relate to dendron generation and the type of linker between the hydrophilic and hydrophobic segment. The synthesized amphiphiles were then characterized for their aggregation behaviour and further evaluated with respect to their siRNA transfection potential by comparing their physico-chemical and biological features. Our findings demonstrated that all four synthesized amphiphiles yielded high gene binding affinities. Furthermore, the ester-linked compounds (G1-Ester-DAPMA, G2-Ester-DAPMA) revealed noticeable gene silencing in vitro without affecting the cell viability in the tumor cell line 786-O. Remarkably, neither G1-Ester-DAPMA nor G2-Ester-DAPMA induced inflammatory side effects after systemic administration in vivo, which is noteworthy because such highly positively charged compounds are typically associated with toxicity concerns which in turn supports their prospective application for in vivo purposes. Therefore, we believe that these structures may serve as new promising alternatives for nonviral siRNA delivery systems and have great potential for further synthetic modifications.

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