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Abstract Photodynamic therapy (PDT) is a promising cancer treatment, but limited oxygen supply in tumors (hypoxia) can hinder its effectiveness. This is because traditional PDT relies on Type‐II reactions that require oxygen. Type‐I photosensitizers (PSs) offer a promising approach to overcome the limitations of tumor photodynamic therapy (PDT) in hypoxic environments. To leverage the advantages of Type‐I PDT, the design and evaluation of a series of Type‐I PSs for developing pure Type‐1 PSs, by incorporating benzene, thiophene, or bithiophene into the donor–acceptor molecular skeleton are reported. Among them, CTTI (with bithiophene) shows the best performance, generating the most superoxide radical (O 2 •− ) upon light irradiation. Importantly, CTTI exclusively produced superoxide radicals, avoiding the less effective Type‐II pathway. This efficiency is due to CTTI's energy gap and low reduction potential, which favor electron transfer to oxygen for O 2 •− generation. Finally, CTTI NPs are successfully fabricated by encapsulating CTTI into liposomes, and validated to be effective in killing tumor cells, even under hypoxic conditions, making them promising hypoxia‐tolerant tumor phototheranostic agents in both in vitro and in vivo applications.
Ding et al. (Sat,) studied this question.