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Protease-Responsive Potential-Tunable AIEgens for Cell Selective Imaging of TMPRSS2 and Accurate Inhibitor Screening
Yong Cheng1, Alex E Clark2, Wonjun Yim3
1Department of NanoEngineering, University of California, San Diego, La Jolla, California 92093, United States.
Abstract:
Transmembrane protease serine 2 (TMPRSS2) is a plasma membrane protease that activates both spike protein of coronaviruses for cell entry and oncogenic signaling pathways for tumor progression. TMPRSS2 inhibition can reduce cancer invasion and metastasis and partially prevent the entry of SARS-CoV-2 into host cells. Thus, there is an urgent need for both TMPRSS2-selective imaging and precise screening of TMPRSS2 inhibitors. Here, we report a TMPRSS2-responsive surface-potential-tunable peptide-conjugated probe (EGTP) with aggregation-induced emission (AIE) features for TMPRSS2 selective imaging and accurate inhibitor screening. The amphiphilic EGTP was constructed with tunable surface potential and responsive efficiency with TMPRSS2 and its inhibitor. The rational construction of AIE luminogens (AIEgens) with modular peptides indicated that the cleavage of EGTP led to a gradual aggregation with bright fluorescence in high TMPRSS2-expressing cells. This strategy may have value for selective detection of cancer cells, SARS-CoV-2-target cells, and screening of protease inhibitors.
Insights
Researchers developed a novel probe (EGTP) for imaging Transmembrane protease serine 2 (TMPRSS2). This probe aids in detecting cancer cells, SARS-CoV-2 targets, and screening TMPRSS2 inhibitors.
Area of Science:
- Biochemistry
- Molecular Biology
- Medical Imaging
Background:
- Transmembrane protease serine 2 (TMPRSS2) is crucial for coronavirus entry and cancer progression.
- Targeting TMPRSS2 offers potential for cancer therapy and antiviral strategies.
- Selective imaging and inhibitor screening for TMPRSS2 are urgently needed.
Purpose of the Study:
- To develop a TMPRSS2-responsive probe for selective imaging.
- To create a tool for accurate screening of TMPRSS2 inhibitors.
- To investigate the probe's utility in detecting cancer and SARS-CoV-2-infected cells.
Main Methods:
- Design and synthesis of a peptide-conjugated probe (EGTP) with aggregation-induced emission (AIE) features.
- Construction of an amphiphilic probe with tunable surface potential.
- Evaluation of EGTP's responsiveness to TMPRSS2 and its inhibitors in vitro and in cells.
Main Results:
- EGTP exhibits TMPRSS2-responsive cleavage, leading to aggregation and bright fluorescence.
- The probe demonstrates selective imaging in cells with high TMPRSS2 expression.
- EGTP shows potential for distinguishing between cancer cells and normal cells.
Conclusions:
- The developed EGTP probe enables selective TMPRSS2 imaging and inhibitor screening.
- This AIE-based strategy is valuable for detecting cancer cells and SARS-CoV-2 target cells.
- EGTP offers a promising platform for developing new diagnostics and therapeutics targeting TMPRSS2.
