Amphiphilic tetracationic porphyrins are exceptionally active antimicrobial photosensitizers : In vitro and in vivo studies with the free-base and Pd-chelate
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim..
Antimicrobial photodynamic inactivation (aPDI) employs the combination of nontoxic photosensitizing dyes and visible light to kill pathogenic microorganisms regardless of drug-resistance, and can be used to treat localized infections. A meso-substituted tetra-methylpyridinium porphyrin with one methyl group replaced by a C12 alkyl chain (FS111) and its Pd-derivative (FS111-Pd) were synthesized and tested as broad-spectrum antimicrobial photosensitizers when excited by blue light (5 or 10 J/cm2 ). Both compounds showed unprecedented activity, with the superior FS111-Pd giving 3 logs of killing at 1 nM, and eradication at 10 nM for Gram-positive methicillin-resistant Staphylococcus aureus. For the Gram-negative Escherichia coli, both compounds produced eradication at 100 nM, while against the fungal yeast Candida albicans, both compounds produced eradication at 500 nM. Both compounds could be categorized as generators of singlet oxygen (ΦΔ = 0.62 for FS111 and 0.71 for FS111-Pd). An in vivo study was carried out using a mouse model of localized infection in a partial thickness skin abrasion caused by bioluminescent Gram-negative uropathogenic E. coli. Both compounds were effective in reducing bioluminescent signal in a dose-dependent manner when excited by blue light (405 nm), but aPDI with FS111-Pd was somewhat superior both during light and in preventing recurrence during the 6 days following PDT.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
Journal of biophotonics - 12(2019), 8 vom: 05. Aug., Seite e201800318 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Xuan, Weijun [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 14.09.2020 Date Revised 14.09.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/jbio.201800318 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM292948425 |
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| 245 | 1 | 0 | |a Amphiphilic tetracationic porphyrins are exceptionally active antimicrobial photosensitizers |b In vitro and in vivo studies with the free-base and Pd-chelate |
| 264 | 1 | |c 2019 | |
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| 500 | |a Date Completed 14.09.2020 | ||
| 500 | |a Date Revised 14.09.2020 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. | ||
| 520 | |a Antimicrobial photodynamic inactivation (aPDI) employs the combination of nontoxic photosensitizing dyes and visible light to kill pathogenic microorganisms regardless of drug-resistance, and can be used to treat localized infections. A meso-substituted tetra-methylpyridinium porphyrin with one methyl group replaced by a C12 alkyl chain (FS111) and its Pd-derivative (FS111-Pd) were synthesized and tested as broad-spectrum antimicrobial photosensitizers when excited by blue light (5 or 10 J/cm2 ). Both compounds showed unprecedented activity, with the superior FS111-Pd giving 3 logs of killing at 1 nM, and eradication at 10 nM for Gram-positive methicillin-resistant Staphylococcus aureus. For the Gram-negative Escherichia coli, both compounds produced eradication at 100 nM, while against the fungal yeast Candida albicans, both compounds produced eradication at 500 nM. Both compounds could be categorized as generators of singlet oxygen (ΦΔ = 0.62 for FS111 and 0.71 for FS111-Pd). An in vivo study was carried out using a mouse model of localized infection in a partial thickness skin abrasion caused by bioluminescent Gram-negative uropathogenic E. coli. Both compounds were effective in reducing bioluminescent signal in a dose-dependent manner when excited by blue light (405 nm), but aPDI with FS111-Pd was somewhat superior both during light and in preventing recurrence during the 6 days following PDT | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a amphiphilic tetracationic porphyrins | |
| 650 | 4 | |a antimicrobial photodynamic inactivation | |
| 650 | 4 | |a bioluminescence imaging | |
| 650 | 4 | |a broad-spectrum activity | |
| 650 | 4 | |a palladium-porphyrin | |
| 650 | 4 | |a uropathogenic Escherichia coli infection | |
| 650 | 7 | |a Anti-Infective Agents |2 NLM | |
| 650 | 7 | |a Chelating Agents |2 NLM | |
| 650 | 7 | |a Photosensitizing Agents |2 NLM | |
| 650 | 7 | |a Porphyrins |2 NLM | |
| 650 | 7 | |a Superoxides |2 NLM | |
| 650 | 7 | |a 11062-77-4 |2 NLM | |
| 650 | 7 | |a Singlet Oxygen |2 NLM | |
| 650 | 7 | |a 17778-80-2 |2 NLM | |
| 650 | 7 | |a Palladium |2 NLM | |
| 650 | 7 | |a 5TWQ1V240M |2 NLM | |
| 700 | 1 | |a Huang, Liyi |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yuguang |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Xiaoqing |e verfasserin |4 aut | |
| 700 | 1 | |a Szewczyk, Grzegorz |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Ying-Ying |e verfasserin |4 aut | |
| 700 | 1 | |a El-Hussein, Ahmed |e verfasserin |4 aut | |
| 700 | 1 | |a Bommer, Jerry C |e verfasserin |4 aut | |
| 700 | 1 | |a Nelson, Mark L |e verfasserin |4 aut | |
| 700 | 1 | |a Sarna, Tadeusz |e verfasserin |4 aut | |
| 700 | 1 | |a Hamblin, Michael R |e verfasserin |4 aut | |
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