4.8 Article

Cell imaging of dopamine receptor using agonist labeling iridium(III) complex

Journal

CHEMICAL SCIENCE
Volume 9, Issue 5, Pages 1119-1125

Publisher

ROYAL SOC CHEMISTRY
DOI: 10.1039/c7sc04798c

Keywords

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Funding

  1. Hong Kong Baptist University [FRG2/15-16/002]
  2. Health and Medical Research Fund [HMRF/14130522, HMRF/14150561]
  3. Research Grants Council [HKBU/12301115, HKBU/204612, HKBU/201913, CityU/11228316]
  4. National Natural Science Foundation of China [21575121, 21628502, 21775131]
  5. Guangdong Province Natural Science Foundation [2015A030313816]
  6. Innovation and Technology Fund [ITS/260/16FX]
  7. Hong Kong Baptist University Century Club
  8. Interdisciplinary Research Matching Scheme [RC-IRMS/15-16/03]
  9. Science and Technology Development Fund, Macao SAR [077/2016/A2]
  10. University of Macau [MYRG2015-00137-ICMS-QRCM, MYRG2016-00151-ICMS-QRCM, MRG044/LCH/2015/ICMS]

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Dopamine receptor expression is correlated with certain types of cancers, including lung, breast and colon cancers. In this study, we report luminescent iridium(III) complexes (11-14) as intracellular dopamine receptor (D1R/D2R) cell imaging agents. Complexes 11 and 13, which are conjugated with a dopamine receptor agonist, showed superior cell imaging characteristics, high stability and low cytotoxicity (> 100 mu M) in A549 lung cancer cells. siRNA knockdown and dopamine competitive assays indicated that complexes 11 and 13 could selectively bind to dopamine receptors (D1R/D2R) in A549 cells. Fluorescence lifetime microscopy demonstrated that complex 13 has a longer luminescence lifetime at the wavelength of 560-650 nm than DAPI and other chromophores in biological fluids. The long luminescence lifetime of complex 13 not only provides an opportunity for efficient dopamine receptor tracking in biological media, but also enables the temporal separation of the probe signal from the intense background signal by fluorescence lifetime microscopy for efficient analysis. Complex 13 also shows high photostability, which could allow it to be employed for long-term cellular imaging. Furthermore, complex 13 could selectively track the internalization process of dopamine receptors (D1R/D2R) in living cells. To the best of our knowledge, complex 13 is the first metal-based compound that has been used to monitor intracellular dopamine receptors in living cells.

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