文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期,新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利:CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

生物合成的低锰含量 MnSe 纳米炸弹激活 cGAS-STING 通路,并诱导免疫原性细胞死亡,增强抗肿瘤免疫。

Biosynthetic MnSe nanobomb with low Mn content activates the cGAS-STING pathway and induces immunogenic cell death to enhance antitumour immunity.

机构信息

School of Pharmacy, Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, Binzhou Medical University, Yantai 264003, PR China.

Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, PR China.

出版信息

Acta Biomater. 2024 Aug;184:383-396. doi: 10.1016/j.actbio.2024.06.025. Epub 2024 Jun 25.


DOI:10.1016/j.actbio.2024.06.025
PMID:38936753
Abstract

Triple-negative breast cancer (TNBC) is a relatively "cold" tumour with low immunogenicity compared to other tumour types. Especially, the immune checkpoint inhibitors to treat metastatic TNBC only shows the modest immune response rates. Here, we used Chlorella vulgaris as a bioreactor to synthesize an efficient nanobomb (Bio-MnSe) aimed at eliciting systemic anti-tumour immune response. Despite possessing extremely low Mn content, Bio-MnSe effectively produced more ROS and activated stronger cGAS-STING signal pathway compared to pure Se nanoparticles and free Mn ions, promoting the infiltration of natural killer (NK) cells, cytotoxic T lymphocytes (CTLs) in tumour, effectively turning "cold" tumour into "hot" tumour, and achieving strong antitumour immunotherapy. Additionally, the use of αPD-L1 as an immune checkpoint antagonist further increased the anti-tumour immune response of Bio-MnSe, resulting in enhanced anti-tumour effects. Doxorubicin (Dox), an immunogenic cell death (ICD) inducer, was combined with Bio-MnSe to form Bio-MnSe@Dox. This Bio-MnSe@Dox not only directly damaged tumour cells and induced tumour ICD but also promoted dendritic cell maturation, cytotoxic T lymphocyte infiltration, and NK cell recruitment, synergistically intensifying anti-tumour immune responses and suppressing tumour relapse and lung metastasis. Collectively, our findings propose an effective strategy for transforming 'cold' tumours to 'hot' ones, thereby advancing the development of anti-tumour immune drugs. STATEMENT OF SIGNIFICANCE: A biogenic MnSe (Bio-MnSe) nanocomposite was synthesized using Chlorella vulgaris as a bioreactor for enhanced immunotherapy of TNBC. Bio-MnSe demonstrated a stronger ability to activate the cGAS-STING signalling pathway and generate more ROS compared to pure Se nanoparticles and free Mn ions. Apoptotic cells induced by Bio-MnSe released a significant amount of interferon, leading to the activation of T and natural killer (NK) cells, ultimately transforming immunologically 'cold' breast tumours to 'hot' tumours and enhancing the tumour's response to immune checkpoint inhibitors. The combination of Bio-MnSe with Dox or αPD-L1 further enhanced the anti-tumour immune response, fostering dendritic cell maturation, infiltration of cytotoxic T lymphocytes, and recruitment of NK cells, thereby enhancing the anti-tumour immunotherapy of TNBC.

摘要

三阴性乳腺癌(TNBC)与其他肿瘤类型相比,免疫原性较低,是一种相对“冷”的肿瘤。特别是,用于治疗转移性 TNBC 的免疫检查点抑制剂仅显示出适度的免疫反应率。在这里,我们使用普通小球藻作为生物反应器来合成一种有效的纳米炸弹(Bio-MnSe),旨在引发全身性抗肿瘤免疫反应。尽管 Bio-MnSe 中 Mn 的含量极低,但与纯硒纳米颗粒和游离 Mn 离子相比,它有效地产生了更多的 ROS,并激活了更强的 cGAS-STING 信号通路,促进了自然杀伤(NK)细胞、细胞毒性 T 淋巴细胞(CTLs)在肿瘤中的浸润,有效地将“冷”肿瘤转化为“热”肿瘤,实现了强大的抗肿瘤免疫治疗。此外,使用 αPD-L1 作为免疫检查点拮抗剂进一步增强了 Bio-MnSe 的抗肿瘤免疫反应,从而增强了抗肿瘤效果。阿霉素(Dox)是一种免疫原性细胞死亡(ICD)诱导剂,与 Bio-MnSe 结合形成 Bio-MnSe@Dox。这种 Bio-MnSe@Dox 不仅直接损伤肿瘤细胞并诱导肿瘤 ICD,还促进树突状细胞成熟、CTL 浸润和 NK 细胞募集,协同增强抗肿瘤免疫反应,抑制肿瘤复发和肺转移。总之,我们的研究结果提出了一种将“冷”肿瘤转化为“热”肿瘤的有效策略,从而推进抗肿瘤免疫药物的发展。

相似文献

[1]
Biosynthetic MnSe nanobomb with low Mn content activates the cGAS-STING pathway and induces immunogenic cell death to enhance antitumour immunity.

Acta Biomater. 2024-8

[2]
Mitochondria-targeted manganese-based mesoporous silica nanoplatforms trigger cGAS-STING activation and sensitize anti PD-L1 therapy in triple-negative breast cancer.

Acta Biomater. 2025-4-26

[3]
Oxygen self-supplying nanoradiosensitizer activates cGAS-STING pathway to enhance radioimmunotherapy of triple negative breast cancer.

J Control Release. 2024-12

[4]
A homologous-targeting cGAS-STING agonist multimodally activates dendritic cells for enhanced cancer immunotherapy.

Acta Biomater. 2024-3-15

[5]
Ultrasound-activated erythrocyte membrane-camouflaged Pt (II) layered double hydroxide enhances PD-1 inhibitor efficacy in triple-negative breast cancer through cGAS-STING pathway-mediated immunogenic cell death.

Theranostics. 2025-1-2

[6]
Manganese is critical for antitumor immune responses via cGAS-STING and improves the efficacy of clinical immunotherapy.

Cell Res. 2020-11

[7]
Facile integration of a binary nano-prodrug with αPD-L1 as a translatable technology for potent immunotherapy of TNBC.

Acta Biomater. 2025-3-1

[8]
Tumor-derived nanovesicles enhance cancer synergistic chemo-immunotherapy by promoting cGAS/STING pathway activation and immunogenetic cell death.

Life Sci. 2024-7-1

[9]
Metal coordination nanotheranostics mediated by nucleoside metabolic inhibitors potentiate STING pathway activation for cancer metalloimmunotherapy.

J Control Release. 2024-6

[10]
Synergistic Induction of Immunogenic Cell Death by Biomineralized Manganese and Bisphosphonates Enhances Anti-PD-L1 Therapy in Triple-Negative Breast Cancer.

Int J Nanomedicine. 2025-4-17

引用本文的文献

[1]
Metal-organic nanostructures based on sono/chemo-nanodynamic synergy of TiO/Ru reaction units: for ultrasound-induced dynamic cancer therapy.

J Nanobiotechnology. 2025-7-21

[2]
Embracing cancer immunotherapy with manganese particles.

Cell Oncol (Dordr). 2025-5-21

[3]
Unraveling the breast cancer tumor microenvironment: crucial factors influencing natural killer cell function and therapeutic strategies.

Int J Biol Sci. 2025-3-24

[4]
Unleashing the Potential of Metal Ions in cGAS-STING Activation: Advancing Nanomaterial-Based Tumor Immunotherapy.

ACS Omega. 2025-3-17

[5]
Advancing the understanding of the role of apoptosis in lung cancer immunotherapy: Global research trends, key themes, and emerging frontiers.

Hum Vaccin Immunother. 2025-12

[6]
The Immunomodulatory Effects of Selenium: A Journey from the Environment to the Human Immune System.

Nutrients. 2024-9-30

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索