Immune-adjuvant loaded Bi₂Se₃ nanocage for photothermal-improved PD-L1 checkpoint blockade immune-tumor metastasis therapy

Checkpoint blockade based immune therapy has shown to be effective but benefit only the minority of patients whose tumors have been pre-infiltrated by T cells. To overcome this obstacles, a PEG-modified Bi₂Se₃ nanocage (NC) loaded with imiquimod (R848), which could efficiently destroy the tumors thus producing enough tumor-associated antigens (TAA) and with the existence of R848, a toll-like-receptor-7 agonist, could generate strong anti-cancer immune responses is reported in this study. Moreover, immunogenic Bi₂Se₃ NC-PEG/R848 mediated photothermal therapy (PTT) sensitizes tumors to checkpoint inhibition mediated by a PD-L1 antibody, not only ablating cancer cells upon NIR laser but also causing strong anti-cancer immunity to suppress distant tumor growth post PTT. Both in vitro and in vivo experiments demonstrate that the Bi₂Se₃ NC-PEG/R848 could effectively activate a PTT-induced immune response as well as silence immune resistance based on PD-L1 checkpoint blockade to ablate the primary tumor and further inhibit the tumor metastasis. Bi₂Se₃ NC reported here exhibits high photothermal conversion efficiency and stability, as well as competent drug loading capacity with large hollow structures and high surface area. Our study not only provides a facial way to synthesize Bi₂Se₃ NC, but also offers an alternative strategy for tumor metastasis.