Molecular engineering to construct thieno[3,2-c]pyridinium based photosensitizers for mitochondrial polarity imaging and photodynamic anticancer therapy

Abstract

Mitochondria are indispensable organelles and have become attractive targets for a lot of diseases. More and more mitochondria targeting photosensitizers (PSs) have been developed for disease diagnosis and photodynamic anticancer therapy. However, current PSs encountered significant limitations, such as short excitation/emission wavelength, low quantum yield (QY), insufficient reactive oxygen species (ROS) generation efficiency. In this study, a series of novel thieno[3,2-c]pyridinium based near-infrared (NIR) aggregation-induced emission PSs (AIE PSs) for targeting mitochondria was rational designed and synthesized by regulating the molecular engineering of D-π-A structure. The synergistic effect of strong D and extended π system fabricated a progressively strong intramolecular charge transfer (ICT) effect to accelerate intersystem crossing (ISC) of excited electrons, which were favorable for the LIQ-TPA-DTZ with NIR emission, good AIE performance, high QY, and high 1O2 and •OH generation efficiency. LIQ-TPA-DTZ can sensitively detect the mitochondrial polarity changes in living cells. Furthermore, it could trigger the mitochondria apoptosis pathway to efficiently photodynamic kill cancer cells and restrain tumor growth in vivo. This work not only provides a powerful tool for mitochondrial targeting imaging and cancer therapy but also offers a facile strategy for constructing thieno[3,2-c] pyridinium based AIE PSs.