Photoactivation-triggered in situ self-supplied H2O2 for boosting chemodynamic therapy via layered double Hydroxide-mediated catalytic cascade reaction

• A photo-activated chemodynamic therapy (CDT) was developed for cancer treatment. • A nanosheet catalyst was constructed to enable cascade catalytic reactions. • Superoxide radicals generated from photodynamic therapy was converted into H 2 O 2 . • In-situ generated and endogenous H 2 O 2 induced ·OH generation for enhanced CDT. Chemodynamic therapy (CDT) has aroused extensive interest as an advanced anti-cancer approach which is featured with high tumor specificity and selectivity. However, chemodynamic therapeutic efficacy heavily relies on the level of endogenous hydrogen peroxide (H 2 O 2 ), which is intrinsically heterogenous and insufficient. Herein, a self-supplied H 2 O 2 enhanced chemodynamic therapeutic strategy is developed by constructing a two-dimensional (2D) sheet-like nanocatalyst to mediate catalytic cascade reactions. The cascade nanocatalyst is fabricated by integrating photosensitizer indocyanine green (ICG) and Fenton reaction catalyst Fe 2+ ions into a 2D ultrathin layered double hydroxide nanoparticles (NPs). Under near infrared light irradiation, ICG not only produces cytotoxic singlet oxygen ( 1 O 2 ) to damage tumor cells, but also generates superoxide radical (O 2 ·- ) that is subsequently converted into H 2 O 2 by reacting with intracellular superoxide dismutase (SOD). A considerable amount of in situ self-supplied H 2 O 2 , together with endogenous H 2 O 2 , is then catalyzed by Fe 2+ released from nanocatalyst to produce abundant, highly cytotoxic hydroxyl radicals ( · OH) to trigger apoptosis and death of tumor cells. In vitro and in vivo evaluations manifest the cascade nanocatalyst-mediated remarkable chemodynamic therapeutic performance. Therefore, this work has demonstrated a cascade catalytic therapeutic nanoplatform enabling photoactivation-triggered H 2 O 2 self-supplied synergistic strategy for safe and efficacious tumor treatment.