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Amplifying Signals via Enzymatic Cascade01:22

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When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
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Activity-Independent Enzyme-Powered Amplification for Improving Signal Stability and Fidelity in Biosensing.

Yibo Zhou1, Shan Hu1, Hong-Wen Liu2

  • 1Hunan Provincial Key Laboratory of Cytochemistry, School of Chemistry and Chemical Engineering, Changsha University of Science and Technology, Changsha 410114, People's Republic of China.

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This study introduces an activity-independent enzyme-powered (AIEP) amplification strategy for biosensing, enhancing signal stability. This novel approach successfully monitored oxidative stress in drug-induced liver injury and evaluated drug efficacy.

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Area of Science:

  • Biomedical Engineering
  • Analytical Chemistry
  • Biochemistry

Background:

  • Enzyme-based signal amplification in biosensing is crucial but limited by environmental factors affecting enzyme activity.
  • Traditional methods suffer from signal instability due to microenvironmental fluctuations (pH, temperature).

Purpose of the Study:

  • To develop an activity-independent enzyme-powered (AIEP) amplification strategy for robust biosensing.
  • To improve signal stability and fidelity in biosensing applications.
  • To monitor oxidative stress in drug-induced liver injury and evaluate therapeutic interventions.

Main Methods:

  • Designed and screened a carboxylesterase (CEs)-configuration-matching fluorophore (CMF).
  • Fabricated a nanobeacon loaded with CMF within an O2•--responsive polymeric micelle.
  • Utilized O2•--triggered nanobeacon degradation for CMF release and subsequent CEs-CMF binding-induced fluorescence, independent of catalytic activity.

Main Results:

  • Successfully monitored oxidative stress associated with drug-induced liver injury.
  • Demonstrated the ability to evaluate the hepatoprotective effects of repair drugs using cell and in vivo imaging.
  • Validated the AIEP strategy for stable and reliable signal generation.

Conclusions:

  • The AIEP strategy offers enhanced signal stability and fidelity for biosensing.
  • This approach is adaptable for various bioactive molecules by modifying the responsive unit.
  • The method provides a versatile platform for pharmacological evaluation and disease monitoring.