Second near-infrared photoactivatable hydrogen selenide nanogenerators for metastasis-inhibited cancer therapy

Abstract Hydrogen selenide (H2Se) plays key roles in diverse physiological processes; however, the noninvasive regulation of H2Se levels in living systems has been rarely achieved and the functional mechanism of H2Se in cancer cells remains unclear. Herein, biocompatible ferrous selenide (FeSe2) nanoflowers with second near-infrared (NIR-Ⅱ) photoactivatable H2Se generation were developed for metastasis-inhibited cancer therapy. Upon NIR-II laser irradiation, FeSe2 nanoflowers generated mild photothermal effect, leading to their decomposition and on-demand release of H2Se to induce cell death. Such a FeSe2 nanoflower-mediated synergistic photothermal-H2Se gas therapy effectively suppressed the tumor growth in a subcutaneous breast tumor-bearing mouse model. Furthermore, the local generation of H2Se was proved to down-regulate the expression levels of metastasis-related proteins, contributing to the complete inhibition of liver and lung metastasis. Overall, we report a NIR-Ⅱ photoactivatable H2Se production strategy for metastasis-inhibiting cancer therapy, which may be mediated by autophagy, opening a new avenue for the biomedical application of H2Se in the future.