Curved corannulene dually targets mitochondria and endoplasmic reticulum, and initiates apoptosis via localized ROS induction upon light triggering.

Organelle-targeting agents are promising in both fundamental and applied biomedicine research, but such materials are very limited. As a curved 2D carbon material, corannulene (Cor) displays an uneven intramolecular electron distribution, producing a large dipole moment that can favor the electrostatic interaction. Based on the large negative mitochondrial membrane potential and the presence of a connection structure between mitochondria and endoplasmic reticulum (ER), we hypothesized that Cor could simultaneously target both mitochondria and ER. Such hypothesis was well validated by using the fluorescence tag-labelled Cor. The co-localization analysis in a model cell line (PC3) revealed a preferred accumulation of Cor in both organelles, as evidenced by a large Pearson correlation coefficient. The large dipole also empowered Cor the ability of controlled production of reactive oxygen species (ROS) upon light irradiation. This feature plus mitochondria targeting of Cor induced depletion of adenosine triphosphate (ATP) and caspase 9/3 activation. The triggered ROS generation in ER caused the calcium dumping in the cytosol, as revealed by a calcium-specific fluorescence probe. A significant degree of apoptosis was induced by Cor as a result of the interplay of dual mitochondria/ER targeting and triggered organelle-specific ROS delivery. This study demonstrated the subcellular targeting ability of Cor for potential ROS-based therapy, and implied that the dipole could be a valuable parameter for efficient design and tailored screening of organelle-targeting materials for various biomedical applications.