Tunable multi-responsive N-heterocyclic carbene-gold nanoenzyme for tumor-specific pyroptosis and immune activation in cancer therapy

IF 13.2 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Nano Today Pub Date : 2024-10-30 DOI:10.1016/j.nantod.2024.102537
Shanshan Liang , Bing Wang , Wei Chen , Tingfeng Zhang , Hao Fang , Minglu Zhang , Si Xu , Zongyi Su , Lingna Zheng , Meng Wang , Xiao He , Weiyue Feng
{"title":"Tunable multi-responsive N-heterocyclic carbene-gold nanoenzyme for tumor-specific pyroptosis and immune activation in cancer therapy","authors":"Shanshan Liang ,&nbsp;Bing Wang ,&nbsp;Wei Chen ,&nbsp;Tingfeng Zhang ,&nbsp;Hao Fang ,&nbsp;Minglu Zhang ,&nbsp;Si Xu ,&nbsp;Zongyi Su ,&nbsp;Lingna Zheng ,&nbsp;Meng Wang ,&nbsp;Xiao He ,&nbsp;Weiyue Feng","doi":"10.1016/j.nantod.2024.102537","DOIUrl":null,"url":null,"abstract":"<div><div>Heterogeneity of the tumor microenvironment (TME) poses significant obstacles to effective tumor treatment. Pyroptosis-based immunogenic cell death (ICD) therapy is an ideal strategy to overcome TME heterogeneity and achieve a satisfactory antitumor effect. However, specific activation of pyroptosis in tumors while sparing normal tissue still remains a great challenge. Here, we have developed novel, biocompatible N-heterocyclic carbenes-gold nanoparticles (NHC@AuNPs) as TME-responsive nanoenzyme and potential pyroptosis inducers through an azide-alkyne cycloaddition “click” reaction and direct aurophilic interaction (Au<sup>I</sup>∙∙∙Au<sup>I</sup>). The NHC@AuNPs demonstrated tunable multi-responsive abilities within the TME, including superior peroxidase (POD) activity, GSH depletion through on-site cleavage Au-Au bond, inhibition of thioredoxin reductase and enhancement of ROS. This ROS buildup damages mitochondria, further enhancing H<sub>2</sub>O<sub>2</sub> release and amplifying the catalytic cycle of ROS production. NHC ligation also exhibited enhanced fusion of NPs with the lipid bilayer, promoting high intracellular uptake in cancer cells. <em>In vitro</em> and <em>in vivo</em> experiments demonstrated that NHC@AuNPs effectively trigger pyroptosis in tumor cells through the ROS-modulated NLRP3/caspase-1/GSDMD pathway and activate antitumor immunity, such as the increased infiltration of CD4<sup>+</sup> and CD8<sup>+</sup> T cells, as well as the significant release of proinflammatory cytokines. These findings provide valuable insights for designing pyroptosis-inducer in cancer therapies.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"59 ","pages":"Article 102537"},"PeriodicalIF":13.2000,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nano Today","FirstCategoryId":"88","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1748013224003931","RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0

Abstract

Heterogeneity of the tumor microenvironment (TME) poses significant obstacles to effective tumor treatment. Pyroptosis-based immunogenic cell death (ICD) therapy is an ideal strategy to overcome TME heterogeneity and achieve a satisfactory antitumor effect. However, specific activation of pyroptosis in tumors while sparing normal tissue still remains a great challenge. Here, we have developed novel, biocompatible N-heterocyclic carbenes-gold nanoparticles (NHC@AuNPs) as TME-responsive nanoenzyme and potential pyroptosis inducers through an azide-alkyne cycloaddition “click” reaction and direct aurophilic interaction (AuI∙∙∙AuI). The NHC@AuNPs demonstrated tunable multi-responsive abilities within the TME, including superior peroxidase (POD) activity, GSH depletion through on-site cleavage Au-Au bond, inhibition of thioredoxin reductase and enhancement of ROS. This ROS buildup damages mitochondria, further enhancing H2O2 release and amplifying the catalytic cycle of ROS production. NHC ligation also exhibited enhanced fusion of NPs with the lipid bilayer, promoting high intracellular uptake in cancer cells. In vitro and in vivo experiments demonstrated that NHC@AuNPs effectively trigger pyroptosis in tumor cells through the ROS-modulated NLRP3/caspase-1/GSDMD pathway and activate antitumor immunity, such as the increased infiltration of CD4+ and CD8+ T cells, as well as the significant release of proinflammatory cytokines. These findings provide valuable insights for designing pyroptosis-inducer in cancer therapies.
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
可调多反应 N-杂环碳金纳米酶,用于肿瘤特异性热休克和癌症治疗中的免疫激活
肿瘤微环境(TME)的异质性是有效治疗肿瘤的重大障碍。基于热蛋白沉积的免疫性细胞死亡疗法(ICD)是克服肿瘤微环境异质性并取得满意抗肿瘤效果的理想策略。然而,如何特异性地激活肿瘤中的热蛋白沉积同时保护正常组织仍然是一个巨大的挑战。在此,我们通过叠氮-炔烃环加成 "点击 "反应和直接亲氨基作用(AuI∙∙∙AuI),开发了新型、生物相容性N-杂环碳烯-金纳米颗粒(NHC@AuNPs),作为TME响应型纳米酶和潜在的热诱变诱导剂。NHC@AuNPs在TME中表现出了可调的多反应能力,包括卓越的过氧化物酶(POD)活性、通过现场裂解Au-Au键消耗GSH、抑制硫代氧化还原酶和增强ROS。这种 ROS 的积累会破坏线粒体,进一步加强 H2O2 的释放并扩大 ROS 生成的催化循环。NHC 连接还能增强 NPs 与脂质双分子层的融合,促进癌细胞的高胞内吸收。体外和体内实验表明,NHC@AuNPs 可通过 ROS 调节的 NLRP3/aspcase-1/GSDMD 通路有效触发肿瘤细胞的热凋亡,并激活抗肿瘤免疫,如增加 CD4+ 和 CD8+ T 细胞的浸润,以及显著释放促炎细胞因子。这些发现为在癌症疗法中设计热诱变诱导剂提供了宝贵的启示。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Nano Today
Nano Today 工程技术-材料科学:综合
CiteScore
21.50
自引率
3.40%
发文量
305
审稿时长
40 days
期刊介绍: Nano Today is a journal dedicated to publishing influential and innovative work in the field of nanoscience and technology. It covers a wide range of subject areas including biomaterials, materials chemistry, materials science, chemistry, bioengineering, biochemistry, genetics and molecular biology, engineering, and nanotechnology. The journal considers articles that inform readers about the latest research, breakthroughs, and topical issues in these fields. It provides comprehensive coverage through a mixture of peer-reviewed articles, research news, and information on key developments. Nano Today is abstracted and indexed in Science Citation Index, Ei Compendex, Embase, Scopus, and INSPEC.
期刊最新文献
Natural-based UV-shielding additives to protect photosensitive pesticides: Production of nanoparticles from the co-self-assembly of lignin and tannin In situ atomic observation of transformation twinning in nanocrystals Energy-based surgery generated carbonized particles promote the development of ovarian cancer Adipose tissue targeted sequential delivery system regulating glycolipid metabolism for systemic obesity and its comorbidities CD33 targeted EzH1 regulated nanotherapy epigenetically inhibits fusion oncoprotein (AML1-ETO) rearranged acute myeloid leukemia in both in vitro and in vivo Patient Derived Xenograft models
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1