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Nitroreductase-Responsive Photosensitizers for Selective Imaging and Photo-Inactivation of Intracellular Bacteria
Wanpeng Zhou1,2, Xuwen Da1, Yao Jian1
1Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, 100190, P.R. China.
Abstract:
Intracellular Staphylococcus aureus (S. aureus), especially the methicillin resistant staphylococcus aureus (MRSA), are difficult to detect and eradicate due to the protection by the host cells. Antibacterial photodynamic therapy (aPDT) offers promise in treating intracellular bacteria, provided that selective damage to the bacteria ranther than host cells can be realized. According to the different nitroreductase (NTR) levels in mammalian cells and S. aureus, herein NTR-responsive photosensitizers (PSs) (T)CyI-NO2 were designed and synthesized. The emission and 1O2 generation of (T)CyI-NO2 are quenched by the 4-nitrobenzyl group, but can be specifically switched on by bacterial NTR. Therefore, selective imaging and photo-inactivation of intracellular S. aureus and MRSA were achieved. Our findings may pave the way for the development of more efficient and selective aPDT agents to combat intractable intracellular infections.
Insights
New photosensitizers target intracellular Staphylococcus aureus (S. aureus) and MRSA. These agents are activated by bacterial nitroreductase, enabling selective imaging and photo-inactivation of bacteria within host cells.
Area of Science:
- Biomedical Engineering
- Photodynamic Therapy
- Infectious Disease Research
Background:
- Intracellular Staphylococcus aureus (S. aureus), including methicillin-resistant S. aureus (MRSA), pose significant treatment challenges due to their protected location within host cells.
- Current methods struggle with effective detection and eradication of these intracellular pathogens.
- Antibacterial photodynamic therapy (aPDT) shows potential but requires selectivity to avoid host cell damage.
Purpose of the Study:
- To design and synthesize novel nitroreductase (NTR)-responsive photosensitizers (PSs) for selective targeting of intracellular S. aureus and MRSA.
- To develop a method for selective imaging and photo-inactivation of intracellular bacteria.
- To explore a new strategy for combating difficult-to-treat intracellular bacterial infections.
Main Methods:
- Design and synthesis of NTR-responsive photosensitizers (T)CyI-NO2, featuring a quenched emission and 1O2 generation.
- Utilizing the differential expression of nitroreductase (NTR) between mammalian cells and S. aureus for targeted activation.
- Demonstrating selective activation of (T)CyI-NO2 by bacterial NTR for imaging and photo-inactivation.
Main Results:
- The synthesized (T)CyI-NO2 photosensitizers exhibited quenched photophysical properties due to a 4-nitrobenzyl group.
- Bacterial NTR specifically activated the emission and 1O2 generation of (T)CyI-NO2.
- Selective imaging and photo-inactivation of intracellular S. aureus and MRSA were successfully achieved using the designed PSs.
Conclusions:
- NTR-responsive photosensitizers offer a promising approach for selectively targeting and eliminating intracellular S. aureus and MRSA.
- This strategy enables selective imaging and photo-inactivation, overcoming limitations of current treatments.
- The findings pave the way for developing advanced aPDT agents against intractable intracellular infections.
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