Multienzyme-Mimicking Nanocomposite for Tumor Phototheranostics and Normal Cell Protection

Selectively regulating the reactive oxygen species (ROS) level in cells by redox modulation with nanoparticles mimicking multiple enzymes holds great promise for protecting normal cells against ROS threats and surpassing the current limitations of ROS-dependent cancer therapy. Herein, we develop a new indocyanine green (ICG)-bovine serum albumin (BSA)-cerium-manganese oxide nanocomposites (IBCM NCs) via facile one-step biomineralization to functionally mimic superoxide dismutase and catalase. IBCM NCs can synergistically regulate superoxide, hydrogen peroxide, oxygen and glutathione levels in cancer cells as well as provide contrast for magnetic resonance imaging. Consequently, cancer hypoxia can be relieved, and the phototherapy efficiency can be dramatically enhanced, leading to a complete ablation of tumor under NIR laser irradiation. On the other hand, IBCM NCs can consume the superoxide and hydrogen peroxide in the normal cells to protect them against ROS threats. Our results demonstrate IBCM NCs can effectively resist ROS threats in normal cells and kill cancer cells through breaking the intracellular redox balance.