Effect of Solubilizing Group on the Antibacterial Activity of Heptamethine Cyanine Photosensitizers
Antibiotic resistance of pathogenic bacteria dictates the development of novel treatment modalities such as antimicrobial photodynamic therapy (APDT) utilizing organic dyes termed photosensitizers that exhibit a high cytotoxicity upon light irradiation. Most of the clinically approved photosensitize...
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MDPI AG
2023-01-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/1/247 |
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| author | Olga Semenova Dmytro Kobzev Iryna Hovor Melad Atrash Faina Nakonechny Olesia Kulyk Andrii Bazylevich Gary Gellerman Leonid Patsenker |
| author_facet | Olga Semenova Dmytro Kobzev Iryna Hovor Melad Atrash Faina Nakonechny Olesia Kulyk Andrii Bazylevich Gary Gellerman Leonid Patsenker |
| author_sort | Olga Semenova |
| collection | DOAJ |
| description | Antibiotic resistance of pathogenic bacteria dictates the development of novel treatment modalities such as antimicrobial photodynamic therapy (APDT) utilizing organic dyes termed photosensitizers that exhibit a high cytotoxicity upon light irradiation. Most of the clinically approved photosensitizers are porphyrins that are poorly excitable in the therapeutic near-IR spectral range. In contrast, cyanine dyes function well in the near-IR region, but their phototoxicity, in general, is very low. The introduction of iodine atoms in the cyanine molecules was recently demonstrated to greatly increase their phototoxicity. Herein, we synthesized a series of the new iodinated heptamethine cyanine dyes (<b>ICy7</b>) containing various solubilizing moieties, i.e., negatively charged carboxylic (<b>ICy7COOH</b>) and sulfonic (<b>ICy7SO<sub>3</sub>H</b>) groups, positively charged triphenylphosphonium (<b>ICy7PPh<sub>3</sub></b>), triethylammonium (<b>ICy7NEt<sub>3</sub></b>) and amino (<b>ICy7NH<sub>2</sub></b>) groups, and neutral amide (<b>ICy7CONHPr</b>) group. The effect of these substituents on the photodynamic eradication of Gram-positive (<i>S. aureus</i>) and Gram-negative (<i>E. coli</i> and <i>P. aeruginosa</i>) pathogens was studied. Cyanine dyes containing the amide and triphenylphosphonium groups were found to be the most efficient for eradication of the investigated bacteria. These dyes are effective at low concentrations of 0.05 µM (33 J/cm<sup>2</sup>) for <i>S. aureus</i>, 50 µM (200 J/cm<sup>2</sup>) for <i>E. coli</i>, and 5 µM (100 J/cm<sup>2</sup>) for <i>P. aeruginosa</i> and considered, therefore, promising photosensitizers for APDT applications. The innovation of the new photosensitizers consisted of a combination of the heavy-atom effect that increases singlet oxygen generation with the solubilizing group’s effect improving cell uptake, and with effective near-IR excitation. Such a combination helped to noticeably increase the APDT efficacy and should pave the way for the development of more advanced photosensitizers for clinical use. |
| first_indexed | 2024-03-09T11:27:27Z |
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| id | doaj.art-4d5f54b02e02412fa923ef02446ea018 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T11:27:27Z |
| publishDate | 2023-01-01 |
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| spelling | doaj.art-4d5f54b02e02412fa923ef02446ea0182023-11-30T23:59:44ZengMDPI AGPharmaceutics1999-49232023-01-0115124710.3390/pharmaceutics15010247Effect of Solubilizing Group on the Antibacterial Activity of Heptamethine Cyanine PhotosensitizersOlga Semenova0Dmytro Kobzev1Iryna Hovor2Melad Atrash3Faina Nakonechny4Olesia Kulyk5Andrii Bazylevich6Gary Gellerman7Leonid Patsenker8Department of Chemical Sciences, Ariel University, Ariel 40700, IsraelDepartment of Chemical Sciences, Ariel University, Ariel 40700, IsraelDepartment of Chemical Sciences, Ariel University, Ariel 40700, IsraelDepartment of Chemical Engineering, Ariel University, Ariel 40700, IsraelDepartment of Chemical Engineering, Ariel University, Ariel 40700, IsraelDepartment of Chemical Sciences, Ariel University, Ariel 40700, IsraelDepartment of Chemical Sciences, Ariel University, Ariel 40700, IsraelDepartment of Chemical Sciences, Ariel University, Ariel 40700, IsraelDepartment of Chemical Sciences, Ariel University, Ariel 40700, IsraelAntibiotic resistance of pathogenic bacteria dictates the development of novel treatment modalities such as antimicrobial photodynamic therapy (APDT) utilizing organic dyes termed photosensitizers that exhibit a high cytotoxicity upon light irradiation. Most of the clinically approved photosensitizers are porphyrins that are poorly excitable in the therapeutic near-IR spectral range. In contrast, cyanine dyes function well in the near-IR region, but their phototoxicity, in general, is very low. The introduction of iodine atoms in the cyanine molecules was recently demonstrated to greatly increase their phototoxicity. Herein, we synthesized a series of the new iodinated heptamethine cyanine dyes (<b>ICy7</b>) containing various solubilizing moieties, i.e., negatively charged carboxylic (<b>ICy7COOH</b>) and sulfonic (<b>ICy7SO<sub>3</sub>H</b>) groups, positively charged triphenylphosphonium (<b>ICy7PPh<sub>3</sub></b>), triethylammonium (<b>ICy7NEt<sub>3</sub></b>) and amino (<b>ICy7NH<sub>2</sub></b>) groups, and neutral amide (<b>ICy7CONHPr</b>) group. The effect of these substituents on the photodynamic eradication of Gram-positive (<i>S. aureus</i>) and Gram-negative (<i>E. coli</i> and <i>P. aeruginosa</i>) pathogens was studied. Cyanine dyes containing the amide and triphenylphosphonium groups were found to be the most efficient for eradication of the investigated bacteria. These dyes are effective at low concentrations of 0.05 µM (33 J/cm<sup>2</sup>) for <i>S. aureus</i>, 50 µM (200 J/cm<sup>2</sup>) for <i>E. coli</i>, and 5 µM (100 J/cm<sup>2</sup>) for <i>P. aeruginosa</i> and considered, therefore, promising photosensitizers for APDT applications. The innovation of the new photosensitizers consisted of a combination of the heavy-atom effect that increases singlet oxygen generation with the solubilizing group’s effect improving cell uptake, and with effective near-IR excitation. Such a combination helped to noticeably increase the APDT efficacy and should pave the way for the development of more advanced photosensitizers for clinical use.https://www.mdpi.com/1999-4923/15/1/247heptamethine cyaninesphotosensitizersantimicrobial photodynamic therapyheavy-atom effectsolubilizing groups |
| spellingShingle | Olga Semenova Dmytro Kobzev Iryna Hovor Melad Atrash Faina Nakonechny Olesia Kulyk Andrii Bazylevich Gary Gellerman Leonid Patsenker Effect of Solubilizing Group on the Antibacterial Activity of Heptamethine Cyanine Photosensitizers Pharmaceutics heptamethine cyanines photosensitizers antimicrobial photodynamic therapy heavy-atom effect solubilizing groups |
| title | Effect of Solubilizing Group on the Antibacterial Activity of Heptamethine Cyanine Photosensitizers |
| title_full | Effect of Solubilizing Group on the Antibacterial Activity of Heptamethine Cyanine Photosensitizers |
| title_fullStr | Effect of Solubilizing Group on the Antibacterial Activity of Heptamethine Cyanine Photosensitizers |
| title_full_unstemmed | Effect of Solubilizing Group on the Antibacterial Activity of Heptamethine Cyanine Photosensitizers |
| title_short | Effect of Solubilizing Group on the Antibacterial Activity of Heptamethine Cyanine Photosensitizers |
| title_sort | effect of solubilizing group on the antibacterial activity of heptamethine cyanine photosensitizers |
| topic | heptamethine cyanines photosensitizers antimicrobial photodynamic therapy heavy-atom effect solubilizing groups |
| url | https://www.mdpi.com/1999-4923/15/1/247 |
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