Targeted NIR-responsive theranostic immuno-nanomedicine combined TLR7 agonist with immune checkpoint blockade for effective cancer photothermal immunotherapy

Abstract

Nanomedicine with immunotherapy offers opportunities to target cancer in an effective manner; however, it remains challenging. We herein report a photothermal material loaded with immune-adjuvant combined immune checkpoint blockade for efficient cancer immunotherapy to target estrogen receptor-positive (ER⁺) breast cancer (BC). Endoxifen (END) expressly targets ER⁺ breast cancer cells. As a proof of concept of a targeting ER⁺ agent, END/NIR-responsive polyaniline (PANi)/a toll-like-receptor-7 agonist imiqumoid (R837) activating immune response co-encapsulated nanoparticles were formed as END-PANi-PVP@R837 NPs and found to be very appropriate as an NIR-responsive photothermal platform for versatile immunogenic cell death (ICD) in combination with an immune checkpoint PD-L1 blockade for development as an immunotherapy strategy. In this study, we concentrate on the therapeutic tactic of combining anti-PD-L1 with NPs, not only ablating cancer cells upon NIR irradiation but also providing strong anti-cancer immunity to destroy tumor progression after treatment. In both in vitro and in vivo experiments it was demonstrated that NPs could efficiently activate PTT to induce an immune response and immune resistance based on the PD-L1 checkpoint to ablate the tumor and inhibit tumor recurrence. We confirm the potency of the NPs, which exhibit high photothermal conversion efficacy and stability. The results demonstrate that the NP combination suppresses tumor cell growth at the tumor margin beyond effective PTT and immunotherapy.