Monitoring the Cellular Delivery of Doxorubicin–Cu Complexes in Cells by Fluorescence Lifetime Imaging Microscopy
- 4 May 2020
- journal article
- research article
- Published by American Chemical Society (ACS) in The Journal of Physical Chemistry A
- Vol. 124 (21), 4235-4240
- https://doi.org/10.1021/acs.jpca.0c00182
Abstract
The information obtained from traditional endpoint biochemical assays in drug studies could provide neither the dynamic processes nor heterogeneous responses of individual cells. In situ imaging microscopy techniques, especially fluorescence lifetime imaging (FLIM) microscopy, could fulfill these requirements. In this work, we used FLIM technique to observe the entry and release of doxorubicin (Dox)-Cu complexes in live KYSE150 cells. The Dox-Cu complex has no fluorescence and measurable lifetime signals as compared to the raw Dox, whose fluorescence could be released by the biothiol compound (such as glutataione). The cell viability results proved the efficiency of Dox-Cu in cells. The FLIM data showed that free doxorubicin was released from Dox-Cu complexes in cytoplasm of KYSE150 cells and then accumulated in the nucleus. The fluorescence lifetime signals reached c.a. 1.21 ns and 1.46 ns in cytoplasm and nucleus after 90-min administration, reflecting the transformation and transportation of Dox-Cu complex. In conclusion, this work provides a satisfactory example for the research of prodrug monitored by FLIM techniques, expanding the useful applications of FLIM technique in drug development.Keywords
Funding Information
- Ministry of Science and Technology of the People's Republic of China (2017YFA0700500)
- China Postdoctoral Science Foundation (2019M663032)
- Department of Education of Guangdong Province (2016KCXTD007)
- National Natural Science Foundation of China (31771584, 61525503, 61620106016, 61835009, 61975127)
- Natural Science Foundation of Guangdong Province (2014A030312008, 2020A1515010679)
- Shenzhen University (2017000193)
- Shenzhen Basic Research Project (JCYJ20170412105003520, JCYJ20170818100153423, JCYJ20170818142804605, JCYJ20180305125304883)
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