Ultrathin 2D As₂Se₃ Nanosheets for Photothermal-Triggered Cancer Immunotherapy

Abstract

Arsenic trioxide (As 2 O 3 ) 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 As 2 Se 3 nanosheets (As 2 Se 3 NSs) with synergistic photothermal-triggered immunotherapy effects. As 2 Se 3 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 As 2 Se 3 NSs by enhancing the infiltration of natural killer cells and effector tumorspecific CD8 + T cells. The synergistic combination of photothermal therapy and immunotherapy driven by As 2 Se 3 NSs via a simple but effective all-in-one strategy achieved efficient anticancer effects, addressing the key limitations of As 2 O 3 for solid tumor treatment. This work demonstrates not only the great potential of selenium for detoxifying arsenic but also the application of 2D As 2 Se 3 nanosheets for cancer therapy.