Enhanced in vitro photodynamic performance under hypoxia-related conditions by BP-Au@MnO₂-Ce6 nanocomposites

Photodynamic therapy (PDT) is a widely used therapeutic strategy that kills tumor cells through singlet oxygen (¹O₂) generated by the combined action of a photosensitizer, oxygen, and light irradiation. However, the efficacy of PDT is often limited by hypoxia, elevated glutathione (GSH) levels in solid tumors, and the hydrophobicity of photosensitizers. Herein, BP-Au@MnO₂-Ce6 nanocomposites based on black phosphorus nanosheets (BPNS) were constructed to enhance photodynamic performance under hypoxia-related conditions in vitro. In the nanocomposites, BPNS serve as both a photosensitive component and a structural platform for the assembly of Au nanoparticles and Ce6 after PEI modification, thereby enhancing light utilization during PDT. MnO₂ can catalyze the decomposition of endogenous H₂O₂ to generate oxygen and can also consume GSH, thereby supporting singlet oxygen generation and reducing the intracellular antioxidant scavenging capacity. The experimental results indicate that the BP-Au@MnO₂-Ce6 nanocomposites enable oxygen generation, GSH depletion, and enhanced ¹O₂ generation. Moreover, the nanocomposites exhibit good biocompatibility and inhibit tumor cell growth in vitro under both normoxic and hypoxic conditions, highlighting their potential as a multifunctional platform for hypoxia-related photodynamic enhancement.