Despite the significant relevance of photodynamic therapy (PDT) as an efficient strategy for anticancer treatment, several challenges compromise its efficiency. Here we report the novel group of tetracyanotetra(aryl)porphyrazine dyes that enable real-time assessment of tissue response and thus predict treatment efficacy. The most remarkable and promising feature of the studied compounds is their belonging to the group of fluorescent molecular rotors. The quantum yield and fluorescence lifetime of the cyanoarylporphyrazines are strongly depend on the local viscosity, so they can be used as intracellular viscosity sensors. The cyanoarylporphyrazines demonstrate high photo-induced toxicity both in vitro and in vivo. Of note, complete recovery from cancer was observed for more than half of the treated animals without any signs of dark toxicity. It was shown that photoinduced cell damage is accompanied by a significant dose-dependent increase in cell viscosity. The viscosity changes under PDT treatment may result from denaturation of macromolecules, inter- and intramolecular crosslinking, membrane disorganization, etc., and reflect the severity of PDT-induced changes in cell physiology. We have proposed the approach for noninvasively measuring the tissue viscosity during the PDT procedure by registering the fluorescence lifetime of the cyanoarylporphyrazines. We believe that the unique properties of the compounds provide a tool for PDT dosimetry and tailoring the PDT treatment regimen to the individual characteristics of each patient.

The work is supported by the Ministry of Science and Higher Education of the Russian Federation (project No. 075-15-2020-927).