Pyroptosis是一种高度炎症性编程细胞死亡，能够激活炎症反应，逆转免疫抑制并促进全身免疫反应，以用于实体肿瘤治疗。然而，不能控制和精确的Pyroptosis刺激过程会导致疗效不足。在这里，我们报道了一种GSH/ROS双重响应纳米凝胶系统（IMs），可以主动靶向肿瘤细胞高表达的甘露糖受体（MR），提供稳定的靛青绿（ICG）光热容量，诱导细胞Pyroptosis并实现增强的肿瘤免疫反应。光触发的IMs通过光活化的ICG诱导细胞质Ca2+内流并激活caspase-3。 SeSe键的断裂可以破坏肿瘤细胞的氧化还原平衡，引起氧化应激，协同增强caspase-3裂解，并最终调节细胞Pyroptosis。与抗程序性死亡受体1（anti-PD-1）结合使用，纳米凝胶系统不仅有效抑制了原发性肿瘤和远处肿瘤，而且延长了小鼠的存活期。本研究介绍了一种优化ICG光热性能并通过触发Pyroptosis增强肿瘤免疫反应的策略，为免疫检查点阻断治疗提供了一个令人印象深刻的选择。版权所有©2023 Elsevier B.V.发布。

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.Copyright © 2023. Published by Elsevier B.V.