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Synthesis of Cationic Amphiphilic Surface-Block Polyester Dendrimers

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Abstract

Cationic amphiphilic polyester dendrimers possessing varied numbers of choline and alkyl chains on the periphery were synthesized and characterized. A combination of divergent and convergent synthetic routes was used to efficiently prepare the dendrimers. All of the amphiphiles bound DNA as determined by an ethidium bromide displacement assay, and the dendrimer that contained two choline and four alkyl chains exhibited the smallest charge ratio. Only this amphiphilic dendrimer formed a well-defined structure alone or with DNA in solution, while the other dendrimer compositions gave aggregates. Specifically, small vesicular structures of several 100 nanometers in diameter were observed with DNA, and this dendrimerplex exhibited the greatest transfection efficiency of the group. The results of this study highlight the important role that charge, hydrophobicity, size, and compaction ability play in binding and formation of DNA-dendrimer complexes and the resulting transfection efficiency.

Graphical Abstract

Cationic amphiphilic polyester dendrimers possessing different numbers of choline heads groups and myristic acid alkyl chains were synthesized and evaluated for gene transfection.

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Acknowledgements

The funding was provided by National Institutes of Health (Grant Nos. R21CA125327, R01GM27278).

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Authors and Affiliations

  1. Departments of Biomedical Engineering and Chemistry, Metcalf Center for Science and Engineering, Boston University, Boston, MA, 02215, USA

    Carla A. H. Prata, Nathanel R. Luman & Mark W. Grinstaff

  2. Department of Biological and Environmental Engineering, Cornell University, Ithaca, NY, 14853, USA

    Yuan Li & Dan Luo

  3. Department of Cell Biology, Duke University Medical Center, Durham, NC, 27710, USA

    Thomas J. McIntosh

  4. INSERM U1212, UMR CNRS 5320, Bordeaux University, Bordeaux, 33076, France

    Philippe Barthélémy

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  1. Carla A. H. Prata
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  2. Nathanel R. Luman
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Correspondence to Mark W. Grinstaff.

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Prata, C.A.H., Luman, N.R., Li, Y. et al. Synthesis of Cationic Amphiphilic Surface-Block Polyester Dendrimers. J Inorg Organomet Polym 28, 383–398 (2018). https://doi.org/10.1007/s10904-017-0651-4

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