Biomimetic catalase-engineered black phosphorus nanosheets enhance photo-/radio-therapy for hepatocellular carcinoma

The hypoxic tumor microenvironment (TME) critically impairs the therapeutic efficacy of photo- and radiotherapy (RT) in hepatocellular carcinoma (HCC). Ameliorating tumor hypoxia thus presents a promising strategy to potentiate these treatment modalities. Herein, we developed a biomimetic nanoplatform by functionalizing black phosphorus nanosheets (BP) with catalase (CAT), forming a stable nanocomposite (BP CAT ) via covalent bonding between carboxyl and hydroxyl groups. To enhance tumor-targeting capability and immune modulation, BP CAT was further camouflaged with macrophage membranes engineered to express anti-PD-L1 single-chain antibodies, yielding α M@BP CAT . This multifunctional construct efficiently catalyzed endogenous hydrogen peroxide into oxygen, thereby relieving intratumoral hypoxia. In vitro and in vivo studies demonstrated that α M@BP CAT preferentially accumulated in HCC tissues, elevated oxygen levels within the TME, and facilitated the infiltration of antitumor immune cells. Consequently, α M@BP CAT significantly sensitized tumors to both phototherapy and RT in an orthotopic HCC mouse model. Collectively, this study presents a novel CAT-delivering BP-based nanoplatform for TME modulation and combinatorial cancer therapy, offering a promising avenue for improving treatment outcomes in HCC.