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

Abstract

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.