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

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 un-controllable 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 Se-Se bonds can break the oxidation and reduction balance of tumor cells, causing oxidative stress and synergistically enhancing caspase-3 cleavage, and regulating cell pyroptosis ultimately. Combined with anti-programmed death receptor 1 (anti-PD-1), the nanogel system not only effectivly suppress both primary tumor and distance tumor but also prolong the survival period of mice. This work introduces a strategy to optimize the photothermal performance of ICG and enhances tumor immune response mediated by triggering pyroptosis, which provides an impressive option for immune check-point blockade therapy.

Automated summary

In this study, a GSH/ROS dual response nanogel system (IMs) was developed to target cancer cells overexpressing the mannose receptor (MR), providing ultra-stable photothermal capacity of indocyanine green (ICG) and inducing cell pyroptosis for enhanced tumor immune response.