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 ORCID:, Checcucci, Alice, Mengoni, Alessio, Morris, Christopher J. ORCID: 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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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
UEA Research Groups: Faculty of Science > Research Groups > Pharmaceutical Materials and Soft Matter
Depositing User: LivePure Connector
Date Deposited: 21 Jul 2020 01:37
Last Modified: 08 Apr 2023 00:01
DOI: 10.1016/j.colsurfb.2020.111266


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