Issue 26, 2022

Dynamic self-assembling supramolecular dendrimer nanosystems as potent antibacterial candidates against drug-resistant bacteria and biofilms

Abstract

The alarming and prevailing antibiotic resistance crisis urgently calls for innovative “outside of the box” antibacterial agents, which can differ substantially from conventional antibiotics. In this context, we have established antibacterial candidates based on dynamic supramolecular dendrimer nanosystems self-assembled with amphiphilic dendrimers composed of a long hydrophobic alkyl chain and a small hydrophilic poly(amidoamine) dendron bearing distinct terminal functionalities. Remarkably, the amphiphilic dendrimer with amine terminals exhibited strong antibacterial activity against both Gram-positive and Gram-negative as well as drug-resistant bacteria, and prevented biofilm formation. Multidisciplinary studies combining experimental approaches and computer modelling together demonstrate that the dendrimer interacts and binds via electrostatic interactions with the bacterial membrane, where it becomes enriched and then dynamically self-assembles into supramolecular nanoassemblies for stronger and multivalent interactions. These, in turn, rapidly promote the insertion of the hydrophobic dendrimer tail into the bacterial membrane thereby inducing bacterial cell lysis and constituting powerful antibacterial activity. Our study presents a novel concept for creating nanotechnology-based antibacterial candidates via dynamic self-assembly and offers a new perspective for combatting recalcitrant bacterial infection.

Graphical abstract: Dynamic self-assembling supramolecular dendrimer nanosystems as potent antibacterial candidates against drug-resistant bacteria and biofilms

Supplementary files

Article information

Article type
Paper
Submitted
27 Apr. 2022
Accepted
14 Maijs 2022
First published
01 Jūn. 2022
This article is Open Access
Creative Commons BY license

Nanoscale, 2022,14, 9286-9296

Dynamic self-assembling supramolecular dendrimer nanosystems as potent antibacterial candidates against drug-resistant bacteria and biofilms

D. Dhumal, B. Maron, E. Malach, Z. Lyu, L. Ding, D. Marson, E. Laurini, A. Tintaru, B. Ralahy, S. Giorgio, S. Pricl, Z. Hayouka and L. Peng, Nanoscale, 2022, 14, 9286 DOI: 10.1039/D2NR02305A

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