Dual-stimulus phototherapeutic nanogel for triggering pyroptosis to promote cancer immunotherapy.

Abstract

Pyroptosis is a highly inflammatory programmed cell death that activates inflammatory response, reverses immunosuppression and promotes systemic immune response for solid tumors treatment. However, the uncontrollable and imprecise process of pyroptosis stimulation leads to a scanty therapeutic effect. Here, we report a GSH/ROS dual response nanogel system (IMs) that can actively target the overexpressed mannose receptor (MR) of cancer cells, serve ultra-stable photothermal capacity of indocyanine green (ICG), induce cell pyroptosis and achieve enhanced tumor immune response. Photo-triggered IMs induce cytoplasmic Ca2+ introgression and activate caspase-3 through photo-activated ICG. The disconnect of SeSe bonds could breaks the oxidation and reduction balance of tumor cells, causing oxidative stress and synergistically enhances caspase-3 cleavage, and regulates cell pyroptosis ultimately. Combined with anti-programmed death receptor 1 (anti-PD-1), the nanogel system not only effective suppressed both primary tumor and distance tumor but also prolonged the survival period of mice. This work introduces a strategy to optimize the photothermal performance of ICG and enhance tumor immune response mediated by triggering pyroptosis, which provides an impressive option for immune checkpoint blockade therapy.