LAUSR

Reversibly controlling the dye arrangements in living systems has great potential to realize spatiotemporally controlled photomedicine. However, tuning or even maintaining a certain arrangement of dyes in a complex living environments is extremely challenging due to the interference of the various biological species. Herein, a conceptual supramolecular strategy to engineer a switchable photosensitizer (PS) via mitochondria‐mediated dynamic interconversion between monomer and J‐aggregation, enabling specific activation of the mitochondria‐targeting photodynamic therapy (PDT) and hibernation after mitochondria damage is presented. The presented mitochondria‐mediated “activate‐then‐hibernate” PS design enables a fascinating spatiotemporally controlled PDT in which spatially controlled mitochondrial‐targeting enhances therapeutic efficacy and temporally controlled activation‐then‐hibernation averts off‐target damage during PDT and tissue damage after clinical treatment, thus offering significant potential for biological research and clinical needs.