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It remains a considerable challenge to realize complete tumor suppression and avoid tumor regrowth by rational design of photosensitizers (PSs) to improve their photon utilization. In this Article, we provide a molecular design (Icy-NBF) based on the oxygen-content-regulated deactivation process of excited states. In the presence of overexpressed nitroreductase in hypoxic cancer cells, Icy-NBF is reduced and converted into a molecule with the same skeleton (Icy-NH2), in which the deactivation of the PS under 808 nm light irradiation proceeds via a different pathway: the excited states deactivation pathway of Icy-NBF involves radiative transition and energy transfer between Icy-NBF and O2; as for Icy-NH2, the deactivation pathway is attributed to non-radiative relaxation. By varying the O2 concentration in tumor cells, the therapeutic mechanism of Icy-NBF under 808 nm light irradiation can be switched between photodynamic and photothermal therapies, which maximizes the advantages of phototherapies with no tumor regrowth. Our study provides help in designing of smart PSs with improvement of photon utilization for efficient tumor photoablation.
Zhao et al. (Fri,) studied this question.