Elucidating the role of surface chemistry on cationic phosphorus dendrimer-siRNA complexation

Nanoscale
Marco A DeriuAndrea Danani

Abstract

In the field of dendrimers targeting small interfering RNA (siRNA) delivery, dendrimer structural properties, such as the flexibility/rigidity ratio, play a crucial role in the efficiency of complexation. However, advances in organic chemistry have enabled the development of dendrimers that differ only by a single atom on their surface terminals. This is the case for cationic phosphorus dendrimers functionalized with either pyrrolidinium (DP) or morpholinium (DM) terminal groups. 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 for 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, an understanding of how small chemical surface changes may completely modify the overall dendrimer-siRNA complexation is a significant breakthrough towards the design of efficient dendrimers for nucleic acid delivery. Herein, we present experimental and computational approaches based on isothermal titration calorimetry and molecular dynamics simulations to elucidate the molecular reasons behind di...Continue Reading

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Citations

Mar 24, 2020·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Zhibo YuElias Fattal
Jun 6, 2020·Molecular Pharmaceutics·Qingqing LiShing Fung Chow
Jan 21, 2021·Journal of Molecular Graphics & Modelling·Michela SpertiLuca Navarini
Dec 8, 2020·Drug Discovery Today·Serge MignaniJean-Pierre Majoral
Feb 1, 2020·Materials Chemistry Frontiers·Yan ZhangOlof Ramström
Aug 18, 2020·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Adam BohrElias Fattal
May 26, 2021·Advanced Drug Delivery Reviews·Elias Fattal, François Fay
Jul 31, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Dayuan WangMingwu Shen

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Methods Mentioned

BETA
isothermal titration calorimetry

Software Mentioned

Linux bash scripts
Origin®
Avogadro chemical editor
Visual Molecular Dynamics ( VMD )
NVT
GROMACS
antechamber

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