肿瘤微环境
炎症体
材料科学
免疫疗法
癌症免疫疗法
癌症研究
髓源性抑制细胞
癌症
免疫系统
炎症
抑制器
医学
免疫学
内科学
作者
Yangyang Zhu,Pin Chen,Bochuan Hu,Suqin Zhong,Kai Yan,Yu Wu,Li S,Yinyin Yang,Zexin Xu,Yutong Lu,Ying Ouyang,Hui Bao,Weiguang Gu,Longping Wen,Yunjiao Zhang
出处
期刊:Biomaterials
[Elsevier]
日期:2024-03-01
卷期号:: 122533-122533
标识
DOI:10.1016/j.biomaterials.2024.122533
摘要
Myeloid-derived suppressor cells (MDSCs) play a crucial role in the immune escape mechanisms that limit the efficacy of immunotherapeutic strategies. In the tumor microenvironment, NLRP3 inflammasome-driven Interleukin-1β (IL-1β) production serves to dampen antitumor immune responses, promoting tumor growth, progression, and immunosuppression. In this study, we revealed that gold nanoparticles (Au NPs) with a size of 30 nm disrupted NLRP3 inflammasome, but not other inflammasomes, in bone marrow-derived macrophages through abrogating NLRP3-NEK7 interactions mediated by reactive oxygen species (ROS). Density functional theory (DFT) calculations provided insights into the mechanism underlying the exceptional ROS scavenging capabilities of Au NPs. Additionally, when coupled with H6, a small peptide targeting MDSCs, Au NPs demonstrated the capacity to effectively reduce IL-1β levels and diminish the MDSCs population in tumor microenvironment, leading to enhanced T cell activation and increased immunotherapeutic efficacy in mouse tumor models that are sensitive and resistant to PD-1 inhibition. Our findings unraveled a novel approach wherein peptide-modified Au NPs relieved the suppressive impact of the tumor microenvironment by inhibiting MDSCs-mediated IL-1β release, which is the first time reported the employing a nanostrategy at modulating MDSCs to reverse the immunosuppressive microenvironment and may hold promise as a potential therapeutic agent for cancer immunotherapy.
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