Second Near‐Infrared Photothermal Semiconducting Polymer Nanoadjuvant for Enhanced Cancer Immunotherapy

Abstract Immunotherapy has offered new treatment options for cancer; however, the therapeutic benefits are often modest and desired to be improved. A semiconducting polymer nanoadjuvant (SPN II R) with a photothermally triggered cargo release for second near‐infrared (NIR‐II) photothermal immunotherapy is reported here. SPN II R consists of a semiconducting polymer nanoparticle core as an NIR‐II photothermal converter, which is doped with a toll‐like receptor (TLR) agonist as an immunotherapy adjuvant and coated with a thermally responsive lipid shell. Upon NIR‐II photoirradiation, SPN II R effectively generates heat not only to ablate tumors and induce immunogenic cell death (ICD), but also to melt the lipid layers for on‐demand release of the TLR agonist. The combination of ICD and activation of TLR7/TLR8 enhances the maturation of dendritic cells, which amplifies anti‐tumor immune responses. Thus, a single treatment of SPN II R‐mediated NIR‐II photothermal immunotherapy effectively inhibits growth of both primary and distant tumors and eliminates lung metastasis in a murine mouse model. This study thus provides a remote‐controlled smart delivery system to synergize photomedicine with immunotherapy for enhanced cancer treatment.