Anticancer Efficacy and Subcellular Site of Action Investigated by Real‐Time Monitoring of Cellular Responses to Localized Drug Delivery in Single Cells

Abstract Subcellular‐targeted drug delivery has much potential to defeat infectious diseases and cancers. Medical and/or biochemical effects of drugs/bioactive molecules delivered to subcellular compartments and their subcellular sites of action need to be investigated but have not been explored. Here the subcellular location‐dependent biochemical responses of a potent anticancer drug, β‐lapachone (β‐lap), is investigated by a reduced graphene oxide (rGO)‐functionalized optical nanoprobe, which can deliver and simultaneously monitor the drug effects at nanoscales. For the first time, distinct oxidative responses and calcium alterations in three selected subcellular domains are observed and clearly pinpoint that the perinuclear region is the optimal subcellular site for β‐lap to have the best anticancer efficacy. The results presented here provide not only scientific insights of subcellular drug–cell interaction that is not obtainable from conventional methods, but they also provide valuable knowledge for rational design of subcellular‐targeted delivery or spatially resolved signal intervention.