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

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 (H2O2), which is intrinsically heterogenous and insufficient. Herein, a self-supplied H2O2 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 Fe2+ ions into a 2D ultrathin layered double hydroxide nanoparticles (NPs). Under near infrared light irradiation, ICG not only produces cytotoxic singlet oxygen (O-1(2)) to damage tumor cells, but also generates superoxide radical (O-2(.-)) that is subsequently converted into H2O2 by reacting with intracellular superoxide dismutase (SOD). A considerable amount of in situ self-supplied H2O2, together with endogenous H2O2, is then catalyzed by Fe2+ 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 chemo-dynamic therapeutic performance. Therefore, this work has demonstrated a cascade catalytic therapeutic nanoplatform enabling photoactivation-triggered H2O2 self-supplied synergistic strategy for safe and efficacious tumor treatment.