Inconvenient dual-laser irradiation and tumor hypoxic environment as well as limited judgment of treating region have impeded the development of combined photothermal and photodynamic therapies (PTT and PDT). Herein, Bi₂Se₃@AIPH nanoparticles (NPs) are facilely developed to overcome these problems. Through a one-step method, free radical generator (AIPH) and phase transition material (lauric acid, LA, 44–46 °C) are encapsulated in hollow bismuth selenide nanoparticles (Bi₂Se₃ NPs). Under a single 808-nm laser irradiation at the tumor area, hyperthermia produced by Bi₂Se₃ not only directly leads to cell death, but also promotes AIPH release by melting LA and triggers free radical generation, which could further eradicate tumor cells in hypoxic environments. Moreover, Bi₂Se₃ with high X-ray attenuation coefficient endows the NPs with high computed tomography (CT) imaging capability, which is important for treating area determination. The results exhibit that Bi₂Se₃@AIPH NPs possesses 31.2% photothermal conversion efficiency for enhanced PTT, ideal free radical generation for oxygen-independent PDT, and 37.77 HU mL mg⁻¹ X-ray attenuation coefficient for CT imaging with high quality. Most importantly, the tumor growth inhibition rate by synergistic PTT, PDT, and following immunotherapy is 99.6%, and even one tumor disappears completely, which demonstrates excellent cascaded synergistic effect of Bi₂Se₃@AIPH NPs for the tumor therapy.

Schematic of irreversible ligand shielding strategy and reversible ligand shielding strategy.