期刊
CHEMICAL ENGINEERING JOURNAL
卷 429, 期 -, 页码 -出版社
ELSEVIER SCIENCE SA
DOI: 10.1016/j.cej.2021.132134
关键词
Drug distribution; Label-free; Magnoflorine; Super-resolution imaging
资金
- National Natural Science Foundation of China [22107059, 21606147, 21305079]
- Academy of Science and Technology Project of Shandong Academy of Medical Sciences [2017-55, 2018-19]
- key projects of industrial science and technology plan in Qiannan prefecture
- Haixi science and technology bureau of Qinghai Province [2017-Q4]
- Academic Promotion Programme of Shandong First Medical University [2019LJ003]
- Development Plan of Shandong Province [2019JZZY010520, 2019GSF108225, 2019GSF107040]
- Jinan Innova-tion Team Project of Colleges and Universities [2019GXRC038]
The study identified a new fluorescent molecule, MF, that allows accurate visualization of drug distribution in organelles without additional labeling strategies using SIM. Through SIM, the researchers explored the localization of MF in mitochondria and its binding target, aiding in understanding the regulatory mechanisms of drugs in various diseases.
In current practice, drug visualization strategies mainly include H-3-or C-14-modification, or dye-labeling steps. Compared to current drug labeling strategies, drug molecules with autofluorescence can achieve accurate visualization of the drug's subcellular distribution. To this end, we screened various compounds in the traditional Chinese medicine compound library and selected a natural, label-free, fluorescent drug molecule named magnoflorine (MF). MF has fluorescent properties and does not require external intervention by the current labeling strategies, thereby proving to be suitable for reporting its distribution in living cells using structured illumination microscopy (SIM). In addition, using SIM, we found that MF not only had a high quantum yield but could also be well localized to the mitochondria. More importantly, the binding target of MF in mitochondria, namely hypochlorite (ClO)(-) was also revealed for the first time at the nanoscale visualization level. Finally, we also found that MF can play a role in binding to the ClO- as a target during fermptosis, hence indicating that MF is a possible intervention drug for this process. In conclusion, we have identified for the first time a new fluorescent molecule, MF, that allows visualizing accurate drug distribution in organelles without additional labeling strategies with SIM. Furthermore, we have discovered the binding target of MF, which is beneficial for understanding of regulatory mechanism of drugs in various diseases.
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