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Updated: Jan 11, 2026
Super-resolution Imaging of the Bacterial Division Machinery
Published on: January 21, 2013
Dual Targeting and Cascaded Aggregation of Luminogen for Washing-Free and Enhanced Fluorescence Imaging of
Yaqing Zhang1,2, Mingrong Wu2, Yue Qi2
1Department of Chemistry, Capital Normal University, Beijing 100048, China.
Abstract:
The invasion and intracellular survival of Staphylococcus aureus (S. aureus) within phagocytic cells is a major cause of serious antibiotic resistance and recurrent infections in clinical settings, making the detection of intracellular S. aureus highly desirable prior to initiating effective treatment. In this study, we proposed a dual-targeting and cascaded aggregation-induced emission luminogen (AIEgen) probe for washing-free and enhanced fluorescence imaging of intracellular S. aureus. The AIEgen probes consist of an AIE molecule (TPE), cleavable peptide (YVADC(StBu)GKK), targeting peptide (RP)3, and the disulfide Cys(StBu) and 2-cyanobenzothiazole (CBT) units, YVADC(StBu)GK(TPE)K(RP)3G-CBT (YTR-CBT). Upon encountering elevated levels of intracellular biomarkers (GSH and Caspase-1) associated with bacterial infection, the YTR-CBT probe undergoes a CBT-Cys click reaction, triggering its self-assembly into AIEgen nanoparticles (TR-CBT-NPs) and consequently activating the AIEgen fluorescence. These nanoparticles then undergo cascaded aggregation on the surface of S. aureusvia the (RP)3 targeting unit, leading to a significantly enhanced fluorescence signal around the intracellular bacteria compared to that of control groups lacking either the targeting unit or bacterial infection. Moreover, the AIEgen probe specifically imaged intracellular bacteria without interference from extracellular bacteria, enabling a washing-free imaging strategy. This capability allowed for rapid monitoring of therapeutic efficacy in a mouse model of septic arthritis involving intracellular bacteria, demonstrating its considerable potential for clinical application.
Insights
A novel dual-targeting probe enables washing-free fluorescence imaging of intracellular Staphylococcus aureus (S. aureus) by activating aggregation-induced emission (AIE) upon encountering infection biomarkers. This allows for enhanced detection and monitoring of antibiotic resistance and recurrent infections.
Area of Science:
- Biomedical Engineering
- Molecular Imaging
- Infectious Diseases
Background:
- Intracellular Staphylococcus aureus (S. aureus) poses challenges due to antibiotic resistance and recurrent infections.
- Effective treatment relies on accurate detection of intracellular S. aureus.
- Current imaging methods often require washing steps, complicating early diagnosis.
Purpose of the Study:
- To develop a novel dual-targeting, cascaded aggregation-induced emission luminogen (AIEgen) probe for enhanced fluorescence imaging of intracellular S. aureus.
- To enable washing-free detection of intracellular S. aureus.
- To assess the probe's potential for monitoring therapeutic efficacy.
Main Methods:
- Design and synthesis of a dual-targeting AIEgen probe (YTR-CBT) incorporating specific peptide sequences and responsive units.
- In vitro activation of the probe via a CBT-Cys click reaction triggered by intracellular biomarkers (GSH and Caspase-1).
- In vitro and in vivo fluorescence imaging of intracellular S. aureus, evaluating probe specificity, signal enhancement, and washing-free capability.
- Application in a mouse model of septic arthritis to monitor therapeutic efficacy.
Main Results:
- The YTR-CBT probe self-assembles into AIEgen nanoparticles (TR-CBT-NPs) upon encountering intracellular infection biomarkers, activating AIE fluorescence.
- Cascaded aggregation of TR-CBT-NPs on S. aureus surfaces via the targeting unit significantly enhanced fluorescence signals.
- The probe achieved specific, washing-free imaging of intracellular bacteria without interference from extracellular bacteria.
- Demonstrated rapid monitoring of therapeutic efficacy in a septic arthritis mouse model.
Conclusions:
- The developed dual-targeting AIEgen probe offers a sensitive and specific washing-free imaging strategy for intracellular S. aureus.
- This approach significantly enhances fluorescence detection, aiding in the diagnosis of antibiotic resistance and recurrent infections.
- The probe shows considerable potential for clinical applications, including real-time monitoring of treatment effectiveness.
