A photo and tumor microenvironment activated nano-enzyme with enhanced ROS generation and hypoxia relief for efficient cancer therapy

Reactive oxygen species (ROS) mediated tumor therapy strategies have exhibited great prospects and attracted increasing attention, among which photodynamic therapy (PDT) has been well-established. However, the anticancer effects of PDT are greatly limited by the hypoxic tumor microenvironment (TME). Hence, exploring a therapeutic strategy that can relieve tumor hypoxia is regarded as the key to overcoming this problem. Herein, we develop a novel nano-enzyme (MnO₂@TPP-PEG) that can accurately conduct tumor-specific catalysis of H₂O₂ to produce oxygen through a Fenton-like reaction, leading to an enhanced PDT under the irradiation of light. More importantly, the process of catalyzing H₂O₂ decomposition at the tumor location can also generate a cytotoxic hydroxyl radical (˙OH), achieving an excellent chemodynamic therapy (CDT) to enhance the ROS mediated anti-cancer effect. Notably, the nano-enzyme exerts a high loading content of the photosensitizer, which minimizes the side effects probably caused by the vector.