Click-Shielded and Targeted Lipopolyplexes

  • Philipp Michael Klein
  • Ernst Wagner
Part of the Methods in Molecular Biology book series (MIMB, volume 2036)


Lipopolyplexes present well-established nucleic acid carriers assembled from sequence-defined cationic lipo-oligomers and DNA or RNA. They can be equipped with additional surface functionality, like shielding and targeting, in a stepwise assembly method using click chemistry. Here, we describe the synthesis of the required compounds, an azide-bearing lipo-oligomer structure and dibenzocyclooctyne (DBCO) click agents as well as the assembly of the compounds with siRNA into a surface-functionalized formulation. Both the lipo-oligomer and the DBCO-equipped shielding and targeting agents are produced by solid-phase synthesis (SPS). This enables for precise variation of all functional units, like variation in the amount of DBCO attachment sites or polyethylene glycol (PEG) length. Special cleavage conditions with only 5% trifluoroacetic acid (TFA) must be applied for the synthesis of the shielding and targeting agents due to acid lability of the DBCO unit. The two-step lipopolyplex assembly technique allows for separate optimization of the core and the shell of the formulation.

Key words

Click chemistry Solid phase synthesis Dibenzocyclooctyne (DBCO) Surface functionalization Lipopolyplexes Nanoparticles Nucleic acid delivery Gene silencing 



This work was supported by DFG SFB1032 B4 (P.K. and E.W.), SFB1066 B5 (P.K. and E.W.), and DFG Excellence Cluster Nanosystems Initiative Munich (E.W.).


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Philipp Michael Klein
    • 1
  • Ernst Wagner
    • 1
    • 2
  1. 1.Pharmaceutical Biotechnology, Center for System-based Drug ResearchLudwig-Maximilians-Universität MünchenMunichGermany
  2. 2.Nanosystems Initiative MunichMunichGermany

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