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Cationic Phenosafranin Photosensitizers Based on Polyhedral Oligomeric Silsesquioxanes for Inactivation of
Krystyna Rozga-Wijas1, Irena Bak-Sypien1, Katarzyna Turecka2
1Centre of Molecular and Macromolecular Studies, Polish Academy of Science, Sienkiewicza 112, 90-363 Lodz, Poland.
Abstract:
The high photodynamic effect of the Newman strain of the S. aureus and of clinical strains of S. aureus MRSA 12673 and E. coli 12519 are observed for new cationic light-activated phenosafranin polyhedral oligomeric silsesquioxane (POSS) conjugates in vitro. Killing of bacteria was achieved at low concentrations of silsesquioxanes (0.38 µM) after light irradiation (λem. max = 522 nm, 10.6 mW/cm2) for 5 min. Water-soluble POSS-photosensitizers are synthesized by chemically coupling a phenosafranin dye (PSF) (3,7-diamino-5-phenylphenazine chloride) to an inorganic silsesquioxane cage activated by attachment of succinic anhydride rings. The chemical structure of conjugates is confirmed by 1H, 13C NMR, HRMS, IR, fluorescence spectroscopy and UV-VIS analyzes. The APDI and daunorubicin (DAU) synergy is investigated for POSSPSFDAU conjugates. Confocal microscopy experiments indicate a site of intracellular accumulation of the POSSPSF, whereas iBuPOSSPSF and POSSPSFDAU accumulate in the cell wall or cell membrane. Results from the TEM study show ruptured S. aureus cells with leaking cytosolic mass and distorted cells of E. coli. Bacterial cells are eradicated by ROS produced upon irradiation of the covalent conjugates that can kill the bacteria by destruction of cellular membranes, intracellular proteins and DNA through the oxidative damage of bacteria.
Insights
New cationic phenosafranin polyhedral oligomeric silsesquioxane (POSS) conjugates demonstrate potent photodynamic antibacterial effects against Staphylococcus aureus and E. coli. These novel POSS-photosensitizers achieve bacterial eradication at low concentrations upon light activation.
Area of Science:
- Materials Science
- Nanotechnology
- Photochemistry
- Antimicrobial Agents
Background:
- Development of novel antimicrobial strategies is crucial to combat antibiotic-resistant bacteria.
- Photodynamic therapy (PDT) offers a light-activated approach to bacterial killing.
- Polyhedral oligomeric silsesquioxanes (POSS) are versatile inorganic nanostructures with tunable properties.
Purpose of the Study:
- To synthesize and characterize novel cationic light-activated phenosafranin polyhedral oligomeric silsesquioxane (POSS) conjugates.
- To evaluate the in vitro photodynamic antibacterial efficacy of these POSS conjugates against Staphylococcus aureus and Escherichia coli.
- To investigate the cellular localization and mechanism of bacterial eradication.
Main Methods:
- Synthesis of water-soluble POSS-photosensitizers by chemically coupling phenosafranin dye (PSF) to POSS cages.
- Structural characterization using NMR, HRMS, IR, fluorescence, and UV-VIS spectroscopy.
- In vitro antibacterial assays involving light irradiation, confocal microscopy, and transmission electron microscopy (TEM).
Main Results:
- High photodynamic antibacterial effect observed for POSS-PSF conjugates against S. aureus and E. coli.
- Bacterial eradication achieved at low POSS concentrations (0.38 µM) after 5 min of light irradiation.
- TEM revealed ruptured bacterial cells, indicating membrane damage and cytosolic leakage.
- Confocal microscopy showed intracellular accumulation of POSSPSF and cell wall/membrane accumulation of POSSPSFDAU.
Conclusions:
- Cationic phenosafranin POSS conjugates are effective photosensitizers for photodynamic antibacterial therapy.
- The conjugates eradicate bacteria via reactive oxygen species (ROS) production, leading to oxidative damage of cellular components.
- These findings highlight the potential of POSS-based nanomaterials as novel antimicrobial agents.
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