Near-Infrared Triggered Cascade of Antitumor Immune Responses Based on the Integrated Core-Shell Nanoparticle

The clinical application of antitumor immunotherapy still faces severe challenges related to efficacy. Here, a light-triggered core-shell nanosystem is designed to boost antitumor immune response via controlled release of anti-PD-L1 (alpha PD-L1) antibodies and enhanced antigen presentation. The nanosystem (AZ-P@P) is constructed via integrating gold nanorods (AuNRs) as a photothermal core and zeolitic imidazolate framework-8 (ZIF-8) as a shell for aPD-L1 delivery, and further PEGylating. In the nanosystem, the ZIF-8 shell protects alpha PD-L1 antibody from the complex physiological environment and hyperthermia. Once accumulated at the tumor site, AZ-P@P under near-infrared (NIR) light-triggered heating induces tumor cell deaths releasing tumor-derived protein antigens (TDPAs) and adenosine triphosphate (ATP). Thereafter, the released ATP degrades the ZIF-8 shell to expose the AuNRs, which can promote intratumoral T cell infiltration by capturing TDPAs and transporting them to dendritic cells (DCs). Concurrently, a large amount of alpha PD-L1 is released in situ to reinvigorate T cell activity. Mechanistic studies reveal that AZ-P@P promotes the maturation of DCs and the infiltration of activated T cells, thus eliciting a robust antitumor immunity. It is demonstrated that AZ-P@P triggered by NIR light can significantly destroy primary tumors and suppress metastasis. This multiple immunoregulatory system provides a promising tool for tumor treatment.