Kinetics-Based Measurement of Hypoxia in Living Cells and Animals Using an Acetoxymethyl Ester Chemiluminescent Probe

Lucas S. Ryan, Jeni Gerberich, Jian Cao, Weiwei An, Becky A. Jenkins, Ralph P Mason, Alexander R. Lippert

Research output: Contribution to journalArticle

Abstract

Oxygenation and tissue hypoxia play critical roles in mammalian biology and contribute to aggressive phenotypes in cancerous tumors, driving research to develop accurate and easy-to-implement methods for monitoring hypoxia in living cells and animal models. This study reports the chemiluminescent probe HyCL-4-AM, which contains a nitroaromatic sensing moiety and, importantly, an acetoxymethyl (AM) ester that dramatically improves operation in cells and animals. HyCL-4-AM provides a selective 60?raquo;000-fold increase in luminescence emission in the presence of rat liver microsomes (RLM). For cellular operation, the chemiluminescence response kinetics is sharply dependent on oxygen levels, enabling highly significant and reproducible measurement of hypoxia in living cells. Whole animal imaging experiments in muscle tissue and tumor xenografts show that HyCL-4-AM can differentiate between well oxygenated muscle tissue and hypoxic tumors, demonstrating potential for monitoring tumor reoxygenation via hyperoxic treatment.

Original languageEnglish (US)
Pages (from-to)1391-1398
Number of pages8
JournalACS Sensors
Volume4
Issue number5
DOIs
StatePublished - May 24 2019

Fingerprint

hypoxia
animals
Tumors
esters
Esters
Animals
tumors
Cells
Kinetics
probes
kinetics
Tissue
muscles
Muscle
phenotype
animal models
Chemiluminescence
Oxygenation
Monitoring
oxygenation

Keywords

  • 1,2-dioxetanes
  • chemiluminescence
  • hypoxia
  • in vivo imaging
  • nitroreductase

ASJC Scopus subject areas

  • Bioengineering
  • Instrumentation
  • Process Chemistry and Technology
  • Fluid Flow and Transfer Processes

Cite this

Kinetics-Based Measurement of Hypoxia in Living Cells and Animals Using an Acetoxymethyl Ester Chemiluminescent Probe. / Ryan, Lucas S.; Gerberich, Jeni; Cao, Jian; An, Weiwei; Jenkins, Becky A.; Mason, Ralph P; Lippert, Alexander R.

In: ACS Sensors, Vol. 4, No. 5, 24.05.2019, p. 1391-1398.

Research output: Contribution to journalArticle

Ryan, Lucas S. ; Gerberich, Jeni ; Cao, Jian ; An, Weiwei ; Jenkins, Becky A. ; Mason, Ralph P ; Lippert, Alexander R. / Kinetics-Based Measurement of Hypoxia in Living Cells and Animals Using an Acetoxymethyl Ester Chemiluminescent Probe. In: ACS Sensors. 2019 ; Vol. 4, No. 5. pp. 1391-1398.
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