Cargando…
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...
Autores principales: | , , , , , , , |
---|---|
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 |
_version_ | 1785083545919684608 |
---|---|
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. |
format | Online Article Text |
id | pubmed-10395270 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT magniarianna amembraneintercalatingmetalfreeconjugatedorganicphotosensitizerforbacterialphotodynamicinactivation AT mattiellosara amembraneintercalatingmetalfreeconjugatedorganicphotosensitizerforbacterialphotodynamicinactivation AT beverinaluca amembraneintercalatingmetalfreeconjugatedorganicphotosensitizerforbacterialphotodynamicinactivation AT mattioligiuseppe amembraneintercalatingmetalfreeconjugatedorganicphotosensitizerforbacterialphotodynamicinactivation AT moschettamatteo amembraneintercalatingmetalfreeconjugatedorganicphotosensitizerforbacterialphotodynamicinactivation AT zucchianita amembraneintercalatingmetalfreeconjugatedorganicphotosensitizerforbacterialphotodynamicinactivation AT paternogiuseppemaria amembraneintercalatingmetalfreeconjugatedorganicphotosensitizerforbacterialphotodynamicinactivation AT lanzaniguglielmo amembraneintercalatingmetalfreeconjugatedorganicphotosensitizerforbacterialphotodynamicinactivation AT magniarianna membraneintercalatingmetalfreeconjugatedorganicphotosensitizerforbacterialphotodynamicinactivation AT mattiellosara membraneintercalatingmetalfreeconjugatedorganicphotosensitizerforbacterialphotodynamicinactivation AT beverinaluca membraneintercalatingmetalfreeconjugatedorganicphotosensitizerforbacterialphotodynamicinactivation AT mattioligiuseppe membraneintercalatingmetalfreeconjugatedorganicphotosensitizerforbacterialphotodynamicinactivation AT moschettamatteo membraneintercalatingmetalfreeconjugatedorganicphotosensitizerforbacterialphotodynamicinactivation AT zucchianita membraneintercalatingmetalfreeconjugatedorganicphotosensitizerforbacterialphotodynamicinactivation AT paternogiuseppemaria membraneintercalatingmetalfreeconjugatedorganicphotosensitizerforbacterialphotodynamicinactivation AT lanzaniguglielmo membraneintercalatingmetalfreeconjugatedorganicphotosensitizerforbacterialphotodynamicinactivation |