An aggregation-induced emission photosensitizer with efficient singlet oxygen generation capacity for mitochondria targeted photodynamic therapy

A family of near-infrared (NIR) aggregation-induced emission (AIE) photosensitizers (PSs) were designed and synthesized to modulate the spectroscopic and photochemical properties of the contained donor-acceptor (D-A) units. Stronger intermolecular charge transfer (ICT) states were promoted by the synergistic action of benzothiadiazoles and quinolines, which accelerates intersystem crossing (ISC). The best NIR AIE-PS, BTQ, showed an extremely high 1O2 generation rate (5.6-fold of Rose Bengal) and highly efficient photodynamic killing of cancer cells. Furthermore, the mechanism by which mitochondria-targeted PSs produce large amounts of reactive oxygen species (ROS) triggering calcium ion (Ca2+) overload and opening of the mitochondrial permeability transition pore (mPTP), thereby disrupting mitochondria and leading to apoptosis, was demonstrated for the first time. This work provides an exciting benchmark for the molecular engineering of AIE-PSs targeting mitochondria and presented new insights of the development of fluorescence imaging guided photodynamic therapy (FL-G-PDT).