NIR-excited superoxide radical procreators to eradicate tumors by targeting the lyso-membrane

Abstract

NIR photosensitizers have been used as potential photo-activators to inhibit cancer cells as well as the growth of various types of bacteria. Herein, we first designed NIR alkylated cationic photosensitizers (Et-NB-C12 > Et-NB-C18 and Mt-NB-C12 > Mt-NB-C18), which target the lyso-membrane for the eradication of tumor cells through prominent superoxide radical generation (type-I PDT) via the lysosome disruption pathway. The O₂⁻˙ radical sensors (DHE and DHR123) exhibited a 10-fold increment in fluorescence intensity in solution and MCF-7 cells after treatment with NIR cationic photosensitizers under 660 nm irradiation. Et-NB-C12 > Et-NB-C18 preferentially targeted the lyso-membrane, resulting in O₂⁻˙ radical generation in the lyso-membranes during PDT irradiation. Furthermore, lysosomal disruption, flow cytometry, and MTT assays demonstrated that the influential generation of O₂⁻˙ radicals in cancer cells initiated cell apoptosis and further cell death after irradiation with PDT light at 660 nm. The inhibition activity of Et-NB-C12 > Et-NB-C18 in MCF-7 cells showed stronger anticancer efficiency (IC₅₀ 0.08 > 0.12 μM) than that of Mt-NB-C12 > Mt-NB-C18 (IC₅₀ = 0.30 > 0.32 μM), lower than that of Ce6 (1.28 μM). In particular, Et-NB-C12 can be effectively utilized in in vivo imaging, and it exhibits outstanding anticancer properties during both ex vivo and in vivo photodynamic therapy.