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Elucidating the Role of Surface Chemistry on Cationic Phosphorus Dendrimer-siRNA Complexation


In the field of dendrimers targeting small interfering RNA (siRNA) delivery, dendrimer structural properties, such as the flexibility/rigidity ratio, play a crucial role on the efficiency of complexation. Nevertheless, advances in organic chemistry has allowed to develop dendrimers which differ only for a single atom on their surface terminals. This is the case of cationic phosphorus dendrimers, functionalized with either pyrrolidinium (DP) or morpholinium (DM) terminal groups, respectively. This small change was shown to strongly affect the dendrimer-siRNA complexation, leading to more efficient anti-inflammatory effects in the case of DP. Reasons of this different behavior can hardly be inferred only by biological in vitro and in vivo experiments due to the high number of variables and complexity of the investigated biological system. However, understanding how small chemical surface changes may completely modify the overall dendrimer-siRNA complexation is a significant breakthrough toward the design of efficient dendrimers for nucleic acids delivery. Here, we present experimental and computational approaches, based on Isothermal Titration Calorimetry and Molecular Dynamics simulations, to elucidate the molecular reasons behind DP and DM different efficiency and activity. Results of the present research highlight how chemical surface modifications may drive the overall dendrimer-siRNA affinity by influencing enthalpic and entropic contributions of the binding free energy. Moreover, this study also elucidates molecular reasons related to complexation stoichiometry which may be crucial in determining dendrimer complexation efficiency.

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Publication details

The article was received on 07 Mar 2018, accepted on 12 May 2018 and first published on 14 May 2018

Article type: Paper
DOI: 10.1039/C8NR01928B
Citation: Nanoscale, 2018, Accepted Manuscript
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    Elucidating the Role of Surface Chemistry on Cationic Phosphorus Dendrimer-siRNA Complexation

    M. A. Deriu, N. Tsapis, M. Noiray, G. Grasso, N. El Brahmi, S. Mignani, J. Majoral, E. Fattal and A. Danani, Nanoscale, 2018, Accepted Manuscript , DOI: 10.1039/C8NR01928B

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