A dual-nanozyme-loaded black phosphorus multifunctional therapeutic platform for combined photothermal/photodynamic/starvation cancer therapy

The typical hypoxia of tumor microenvironments seriously affects the efficacy of starvation therapy (ST) and photodynamic therapy (PDT). Therefore, it is of great significance to prepare a multimodal combined therapy nanocomposite with the ability to relieve tumor hypoxia. It is an effective method to release oxygen into the tumor microenvironment using a nanoenzyme. In this work, two-dimensional black phosphorus nanosheets (BPNSs) were used as photothermal reagents and photosensitized agents due to the unique physical properties and also used as nano-carriers for the in situ reduction deposition of Au nanoparticles and fragmented MnO2 coatings. Finally, polyethylene glycol was introduced to obtain the nanocomposite BP@Au@MnO2-PEG (i.e., AMGP). In the tumor microenvironment, MnO2 can catalyze endogenous H2O2 to produce oxygen, improving the effect of ST and PDT. H2O2 generated via the catalytic oxidation of glucose by Au nanoparticles can continue to be used as the substrate catalyzed by MnO2. Meanwhile, black phosphorus nanosheets have excellent photothermal properties for photothermal treatment. The results of in vitro and in vivo experiments indicated that AMGP nanocomposites have good combined antitumor efficacies and biosafety.