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New glucose sensors offer enhanced monitoring of liver spheroids for drug safety testing. These tools aid in predicting drug-induced liver injury using organ-on-a-chip models during early drug development.

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Area of Science:

  • Biomedical Engineering
  • Analytical Chemistry
  • Hepatology

Background:

  • Liver 3D cell models are crucial for predicting drug metabolic safety by monitoring physiological markers like glucose.
  • Existing ortho-aminomethyl phenylboronic acid (PDBA) glucose sensors, including Mc-CDBA, have limitations in monitoring glucose within spheroids.
  • Accurate intra- and extracellular glucose monitoring is essential for assessing drug-induced liver toxicity.

Purpose of the Study:

  • To develop novel Mc-CDBA derivatives for precise intra- and extracellular glucose monitoring in liver spheroids.
  • To evaluate the efficacy of these new sensors in detecting drug-induced toxicity.
  • To establish advanced organ-on-a-chip applications for early drug development.

Main Methods:

  • Synthesis of carboxylic (BA) and amide (BA 5)-based Mc-CDBA glucose sensor derivatives.
  • Assessment of spectroscopic properties and glucose sensitivity of the novel sensors.
  • Evaluation of intracellular accumulation and fluorescence sensitivity of BA 5 in liver spheroids.
  • Development of a hydrogel-embedded extracellular sensor (HG-BA 21) for continuous monitoring.

Main Results:

  • Developed BA and BA 5 sensors exhibit superior spectroscopic features for glucose detection.
  • BA 5 demonstrates selective intracellular accumulation in liver spheroids with over 3-fold higher basal fluorescence sensitivity than Mc-CDBA.
  • HG-BA 21 enables extracellular glucose monitoring under simulated physiological flow conditions.
  • The developed sensors are effective for liver spheroid assays and organ-on-a-chip applications.

Conclusions:

  • The novel Mc-CDBA derivatives (BA, BA 5, HG-BA 21) provide powerful tools for intra- and extracellular glucose monitoring.
  • These sensors enhance the predictive capability of liver 3D cell models for drug-induced liver injury.
  • The developed sensors represent a significant advancement for organ-on-a-chip technology in early drug development and safety assessment.