Super-resolution image-based tracking of drug distribution in mitochondria of a label-free naturally derived drug molecules

In current practice, drug visualization strategies mainly include 3H-or 14C-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 ferroptosis, 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.