Key Laboratory of Luminescence Analysis and Molecular Sensing, Ministry of Education, School of Materials and Energy & Chongqing Engineering Research Center for Micro-Nano Biomedical Materials and Devices, Southwest University, Chongqing 400715, PR China.
State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile and Biomass Sciences, Southwest University, Chongqing 400715, PR China.
J Control Release. 2023 Jun;358:219-231. doi: 10.1016/j.jconrel.2023.04.030. Epub 2023 May 4.
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 Ca introgression and activate caspase-3 through photo-activated ICG. The disconnect of SeSe 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 checkpoint blockade therapy.
细胞焦亡是一种高度炎症性的程序性细胞死亡，可激活炎症反应、逆转免疫抑制并促进实体瘤的全身免疫反应。然而，细胞焦亡刺激的不可控和不精确过程导致治疗效果不佳。在这里，我们报告了一种 GSH/ROS 双重响应纳米凝胶系统（IMs），它可以主动靶向癌细胞过度表达的甘露糖受体（MR），具有超稳定的吲哚菁绿（ICG）光热能力，诱导细胞焦亡并实现增强的肿瘤免疫反应。光触发的 IMCs 通过光激活的 ICG 诱导细胞质 Ca 内流并激活 caspase-3。SeSe 键的断裂会打破肿瘤细胞的氧化还原平衡，导致氧化应激，并协同增强 caspase-3 的切割，最终调节细胞焦亡。与抗程序性死亡受体 1（抗 PD-1）联合使用，纳米凝胶系统不仅有效地抑制了原发肿瘤和远处肿瘤，还延长了小鼠的生存期。这项工作介绍了一种优化 ICG 光热性能并通过触发细胞焦亡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种有吸引力的选择。
