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A membrane intercalating metal-free conjugated organic photosensitizer for bacterial photodynamic inactivation

Photodynamic inhibition (PDI) of bacteria represents a powerful strategy for dealing with multidrug-resistant pathogens and infections, as it exhibits minimal development of antibiotic resistance. The PDI action stems from the generation of a triplet state in the photosensitizer (PS), which subseque...

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Autores principales: Magni, Arianna, Mattiello, Sara, Beverina, Luca, Mattioli, Giuseppe, Moschetta, Matteo, Zucchi, Anita, Paternò, Giuseppe Maria, Lanzani, Guglielmo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10395270/
https://www.ncbi.nlm.nih.gov/pubmed/37538813
http://dx.doi.org/10.1039/d3sc01168b
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author Magni, Arianna
Mattiello, Sara
Beverina, Luca
Mattioli, Giuseppe
Moschetta, Matteo
Zucchi, Anita
Paternò, Giuseppe Maria
Lanzani, Guglielmo
author_facet Magni, Arianna
Mattiello, Sara
Beverina, Luca
Mattioli, Giuseppe
Moschetta, Matteo
Zucchi, Anita
Paternò, Giuseppe Maria
Lanzani, Guglielmo
author_sort Magni, Arianna
collection PubMed
description Photodynamic inhibition (PDI) of bacteria represents a powerful strategy for dealing with multidrug-resistant pathogens and infections, as it exhibits minimal development of antibiotic resistance. The PDI action stems from the generation of a triplet state in the photosensitizer (PS), which subsequently transfers energy or electrons to molecular oxygen, resulting in the formation of reactive oxygen species (ROS). These ROS are then able to damage cells, eventually causing bacterial eradication. Enhancing the efficacy of PDI includes the introduction of heavy atoms to augment triplet generation in the PS, as well as membrane intercalation to circumvent the problem of the short lifetime of ROS. However, the former approach can pose safety and environmental concerns, while achieving stable membrane partitioning remains challenging due to the complex outer envelope of bacteria. Here, we introduce a novel PS, consisting of a metal-free donor–acceptor thiophene-based conjugate molecule (BV-1). It presents several advantageous features for achieving effective PDI, namely: (i) it exhibits strong light absorption due to the conjugated donor–acceptor moieties; (ii) it exhibits spontaneous and stable membrane partitioning thanks to its amphiphilicity, accompanied by a strong fluorescence turn-on; (iii) it undergoes metal-free intersystem crossing, which occurs preferentially when the molecule resides in the membrane. All these properties, which we rationalized via optical spectroscopies and calculations, enable the effective eradication of Escherichia coli, with an inhibition concentration that is below that of current state-of-the-art treatments. Our approach holds significant potential for the development of new PS for controlling bacterial infections, particularly those caused by Gram-negative bacteria.
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spelling pubmed-103952702023-08-03 A membrane intercalating metal-free conjugated organic photosensitizer for bacterial photodynamic inactivation Magni, Arianna Mattiello, Sara Beverina, Luca Mattioli, Giuseppe Moschetta, Matteo Zucchi, Anita Paternò, Giuseppe Maria Lanzani, Guglielmo Chem Sci Chemistry Photodynamic inhibition (PDI) of bacteria represents a powerful strategy for dealing with multidrug-resistant pathogens and infections, as it exhibits minimal development of antibiotic resistance. The PDI action stems from the generation of a triplet state in the photosensitizer (PS), which subsequently transfers energy or electrons to molecular oxygen, resulting in the formation of reactive oxygen species (ROS). These ROS are then able to damage cells, eventually causing bacterial eradication. Enhancing the efficacy of PDI includes the introduction of heavy atoms to augment triplet generation in the PS, as well as membrane intercalation to circumvent the problem of the short lifetime of ROS. However, the former approach can pose safety and environmental concerns, while achieving stable membrane partitioning remains challenging due to the complex outer envelope of bacteria. Here, we introduce a novel PS, consisting of a metal-free donor–acceptor thiophene-based conjugate molecule (BV-1). It presents several advantageous features for achieving effective PDI, namely: (i) it exhibits strong light absorption due to the conjugated donor–acceptor moieties; (ii) it exhibits spontaneous and stable membrane partitioning thanks to its amphiphilicity, accompanied by a strong fluorescence turn-on; (iii) it undergoes metal-free intersystem crossing, which occurs preferentially when the molecule resides in the membrane. All these properties, which we rationalized via optical spectroscopies and calculations, enable the effective eradication of Escherichia coli, with an inhibition concentration that is below that of current state-of-the-art treatments. Our approach holds significant potential for the development of new PS for controlling bacterial infections, particularly those caused by Gram-negative bacteria. The Royal Society of Chemistry 2023-07-05 /pmc/articles/PMC10395270/ /pubmed/37538813 http://dx.doi.org/10.1039/d3sc01168b Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/
spellingShingle Chemistry
Magni, Arianna
Mattiello, Sara
Beverina, Luca
Mattioli, Giuseppe
Moschetta, Matteo
Zucchi, Anita
Paternò, Giuseppe Maria
Lanzani, Guglielmo
A membrane intercalating metal-free conjugated organic photosensitizer for bacterial photodynamic inactivation
title A membrane intercalating metal-free conjugated organic photosensitizer for bacterial photodynamic inactivation
title_full A membrane intercalating metal-free conjugated organic photosensitizer for bacterial photodynamic inactivation
title_fullStr A membrane intercalating metal-free conjugated organic photosensitizer for bacterial photodynamic inactivation
title_full_unstemmed A membrane intercalating metal-free conjugated organic photosensitizer for bacterial photodynamic inactivation
title_short A membrane intercalating metal-free conjugated organic photosensitizer for bacterial photodynamic inactivation
title_sort membrane intercalating metal-free conjugated organic photosensitizer for bacterial photodynamic inactivation
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10395270/
https://www.ncbi.nlm.nih.gov/pubmed/37538813
http://dx.doi.org/10.1039/d3sc01168b
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