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

Dinesh Dhumal, Bar Maron, Einav Malach, Zhenbin Lyu, Ling Ding, Domenico Marson, Erik Laurini, Aura Tintaru, Brigino Ralahy, Suzanne Giorgio, Sabrina Pricl, Zvi Hayouka*, Ling Peng*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

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.

Original languageAmerican English
Pages (from-to)9286-9296
Number of pages11
JournalNanoscale
Volume14
Issue number26
DOIs
StatePublished - 1 Jun 2022

Bibliographical note

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© 2022 The Royal Society of Chemistry.

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