NIR Light‐Driven Bi₂Se₃‐Based Nanoreactor with “Three in One” Hemin‐Assisted Cascade Catalysis for Synergetic Cancer Therapy

Abstract Photocatalytic semiconductor‐based nanoreactors, that convert nontoxic molecules into toxic ones for cancer therapy, have attracted great interest. However, its therapeutic efficiency is limited by the fast electron–hole recombination within a narrow bandgap, low oxidative damage of H₂O₂^, and tumor hypoxia. Herein, aggregation‐limited hemin is introduced onto Bi₂Se₃ nanoparticles for successively solving these problems. The nanoreactor (Bi₂Se₃@hemin‐(G‐H)‐HA NPs) is obtained through adamantane modified hemin and β‐cyclodextrin modified hyaluronic acid complexing and wrapping on Bi₂Se₃ NPs via host–guest and electrostatic interaction. Once irradiated by NIR light, the hemin assists Bi₂Se₃ to separate electron–hole pairs and catalyze endogenous H₂O to generate vast H₂O₂, resulting in a 3.9‐fold higher H₂O₂ generation than that of individual Bi₂Se₃. Subsequently, H₂O₂ is catalyzed by aggregation‐limited hemin to generate highly toxic •OH and •O₂⁻, which improves the total reactive oxygen species generation of Bi₂Se₃@hemin‐(G‐H)‐HA by 10.8‐fold compared to that of Bi₂Se₃ NPs. Importantly, the cytotoxicity result exhibits a death rate of HepG2 cells of above 90%, even though in a simulated hypoxic environment. Additionally, the in vivo result indicates this nanoreactor realizes an synergetic anticancer effect with a tumor inhibition rate of 92.3%. Overall, such a nanoreactor with hemin‐assisted cascade catalysis is a promising candidate for improving therapeutic efficacy.