Ultrathin 2D As₂Se₃ Nanosheets for Photothermal-Triggered Cancer Immunotherapy

Arsenic trioxide (As₂O₃) has achieved groundbreaking success in the treatment of acute promyelocytic leukemia (APL). However, its toxic side effects seriously limit its therapeutic application in the treatment of solid tumors. To detoxify the severe side effects of arsenic, herein we synthesized innovative 2D ultrathin As₂Se₃ nanosheets (As₂Se₃ NSs) with synergistic photothermal-triggered immunotherapy effects. As₂Se₃ NSs are biocompatible and biodegradable under physiological conditions and can release As(III) and Se(0). Furthermore, selenium increases the immunomodulatory efficacy of arsenic treatments, facilitating reprogramming of the tumor microenvironment by As₂Se₃ NSs by enhancing the infiltration of natural killer cells and effector tumor-specific CD8⁺ T cells. The synergistic combination of photothermal therapy and immunotherapy driven by As₂Se₃ NSs via a simple but effective all-in-one strategy achieved efficient anticancer effects, addressing the key limitations of As₂O₃ for solid tumor treatment. This work demonstrates not only the great potential of selenium for detoxifying arsenic but also the application of 2D As₂Se₃ nanosheets for cancer therapy.