Multifunctional nanoassemblies target bacterial lipopolysaccharides for enhanced antimicrobial DNA delivery

Montis, Costanza, Joseph, Pierre, Magnani, Chiara, Marín-Menéndez, Alejandro, Barbero, Francesco, Ruiz Estrada, Amalia, Nepravishta, Ridvan, Angulo, Jesus, Checcucci, Alice, Mengoni, Alessio, Morris, Christopher J. and Berti, Debora (2020) Multifunctional nanoassemblies target bacterial lipopolysaccharides for enhanced antimicrobial DNA delivery. Colloids and Surfaces B: Biointerfaces, 195. ISSN 0927-7765

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Abstract

The development of new therapeutic strategies against multidrug resistant Gram-negative bacteria is a major challenge for pharmaceutical research. In this respect, it is increasingly recognized that an efficient treatment for resistant bacterial infections should combine antimicrobial and anti-inflammatory effects. Here, we explore the multifunctional therapeutic potential of nanostructured self-assemblies from a cationic bolaamphiphile, which target bacterial lipopolysaccharides (LPSs) and associates with an anti-bacterial nucleic acid to form nanoplexes with therapeutic efficacy against Gram-negative bacteria. To understand the mechanistic details of these multifunctional antimicrobial-anti-inflammatory properties, we performed a fundamental study, comparing the interaction of these nanostructured therapeutics with synthetic biomimetic bacterial membranes and live bacterial cells. Combining a wide range of experimental techniques (Confocal Microscopy, Fluorescence Correlation Spectroscopy, Microfluidics, NMR, LPS binding assays), we demonstrate that the LPS targeting capacity of the bolaamphiphile self-assemblies, comparable to that exerted by Polymixin B, is a key feature of these nanoplexes and one that permits entry of therapeutic nucleic acids in Gram-negative bacteria. These findings enable a new approach to the design of efficient multifunctional therapeutics with combined antimicrobial and anti-inflammatory effects and have therefore the potential to broadly impact fundamental and applied research on self-assembled nano-sized antibacterials for antibiotic resistant infections.

Item Type: Article
Faculty \ School: Faculty of Science > School of Pharmacy
Depositing User: LivePure Connector
Date Deposited: 21 Jul 2020 01:37
Last Modified: 31 Aug 2020 23:54
URI: https://ueaeprints.uea.ac.uk/id/eprint/76200
DOI: 10.1016/j.colsurfb.2020.111266

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