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Journal Articles Colloids and Surfaces B: Biointerfaces Year : 2020

Multifunctional nanoassemblies target bacterial lipopolysaccharides for enhanced antimicrobial DNA delivery

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.
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Dates and versions

hal-02949343 , version 1 (06-11-2020)

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Costanza Montis, Pierre Joseph, Chiara Magnani, Alejandro Marín-Menéndez, Francesco Barbero, et al.. Multifunctional nanoassemblies target bacterial lipopolysaccharides for enhanced antimicrobial DNA delivery. Colloids and Surfaces B: Biointerfaces, 2020, 195, pp.111266. ⟨10.1016/j.colsurfb.2020.111266⟩. ⟨hal-02949343⟩
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