A Simple Route toward Next-Generation Thiobase-Based Photosensitizers for Cancer Theranostics

Sulfur-substituted
biocompatible carbonyl fluorophores have been
recognized as effective heavy-atom-free photosensitizers (PSs) for
cancer therapy due to their remarkable phototherapeutic properties.
However, guidelines on their molecular design are still a substantial
challenge. Most of the existing thiocarbonyl-based PSs are nonemissive
in both the solution and restricted states, which hinders their further
biomedical applications. Herein, we report the interesting finding
that sulfur-substituted coumarins exhibit an uncommon phenomenon,
aggregation-induced emission. More intriguingly, we also found that
the introduction of a strong electron-accepting trifluoromethyl group
is crucial to facilitate the mitochondrial-targeting ability of neutral
coumarin fluorophores. The resulting CMS-2 PS displayed selective
imaging of mitochondria and exhibited much higher photodynamic therapy
efficiency toward cancer cells than that of the commercial PS erythrosine
B. This work provides deep insight into the molecular design of heavy-atom-free
thiobase-based PSs and simultaneously offers a great opportunity to
develop novel mitochondrial-targeting fluorescent indicators with
neutral bioinspired platforms.