Bioeliminable Pt@Bi₂Se₃-RGD Nanoassembly for Enhancing Photoacoustic Imaging-Guided Tumor Immuno-Radiotherapy by Inducing Apoptosis via the Areg Pathway

<b>Background:</b> Nanoradiosensitizers containing high Z-group elements have been reported widely as potential candidates for radiotherapy. However, the specific regulatory mechanism is unclear, and biodegradability needs to be addressed urgently. <b>Methods:</b> We synthesized a silk sericin-containing nano assembly, Pt@Bi₂Se₃-RGD (PBR). PBR's antitumor and bioeliminable effects were demonstrated in 4T1 tumor cells <i>in vitro</i> and <i>in vivo</i>. The immuno-radiotherapy effects of PBR were evaluated using a bilateral tumor model. <b>Results:</b> Combining photoacoustic imaging-guided PBR with radiotherapy improved the efficiency of anti-PD-L1 treatment, eliciting a robust immune response. Importantly, silk sericin-containing PBR could respond to the local intracellular environment in the tumor with acidic pH and overexpressed MMP-9, collapsing into Bi, Se, and scattered Pt nanoparticles (NPs) and finally be cleared from the body. The results also suggested that PBR may act on the Areg/Egfr/Bcl-2 pathway, inducing apoptosis for radiosensitization. <b>Conclusion:</b> The multifunctional, bioeliminable PBR nanoassembly synthesized in this study demonstrated radiosensitization, which, in conjunction with the PD-L1 immune blockade, could suppress primary and distal tumors. Thus, as a sensitizer for synergistic radiotherapy and immunotherapy, PBR could have wide-ranging clinical applications in oncology.