RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
荧光肽调控的 2D ZnO/MnO(2) 纳米片异质结构可实现肿瘤对免疫治疗早期反应的监测
英文原题：Fluorogenic Peptide-Modulated 2D ZnO/MnO(2) Nanosheet Heterostructure Enables Monitoring of Tumor Early Response to Immunotherapy.
查看英文原题
Fluorogenic Peptide-Modulated 2D ZnO/MnO(2) Nanosheet Heterostructure Enables Monitoring of Tumor Early Response to Immunotherapy.
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中文摘要
实时监测自然杀伤（NK）细胞的过继转移对于评估癌症免疫治疗的疗效至关重要。然而，目前尚无有效策略在体内验证NK细胞的活性。在此，我们开发了一种可激活纳米传感器，用于可视化过继NK细胞的体内活性。该纳米传感器由二维ZnO/MnO₂纳米片异质结构（ZnO/MnO₂）组成，并修饰了荧光肽（Pep-ZnO/MnO₂），其中颗粒酶B（Gzm B）可切割的肽序列与荧光染料和淬灭剂对偶联。细胞内吞后，细胞内高浓度的谷胱甘肽（GSH）破坏ZnO/MnO₂并解离荧光肽。GSH还原产生的Mn²⁺可用作磁共振成像（MRI）造影剂。Gzm B切割肽序列，为Gzm B的活性提供荧光“开启”检测。所制备的纳米传感器能够实现原位成像并监测Gzm B介导的NK细胞对癌细胞的应答。此外，该纳米传感器还可用于评估基于NK细胞的免疫疗法在体内的疗效。
展开英文摘要原文
Real-time monitoring of the adoptive transfer of natural killer (NK) cells is crucial for evaluating the efficacy of cancer immunotherapy.
However, no effective strategy to verify the activity of NK cells in vivo.
Herein, we developed an activatable nanosensor to visualize the in vivo activity of adoptive NK cells. The nanosensor consists of a 2D ZnO/MnO 2 nanosheet heterostructure (ZnO/MnO 2 ) modified with a fluorogenic peptide (Pep-ZnO/MnO 2 ), in which a granzyme B (Gzm B)-cleavable peptide sequence was conjugated with a fluorescent dye and a quencher pair.
Upon cell endocytosis, the intracellular high concentration of glutathione (GSH) destroys the ZnO/MnO 2 and disassembles the fluorogenic peptide. The reduced Mn 2+ by GSH can be used as a magnetic resonance imaging (MRI) contrast agent. Gzm B cleaves the peptide sequence, providing a fluorescence "turn-on" assay for the activity of Gzm B. The as-prepared nanosensor enables in situ imaging and monitoring of the Gzm B-mediated NK cell responses against cancer cells.
Furthermore, the nanosensor can also be used to evaluate the efficacy of NK cell-based immunotherapies in vivo.
论文信息
- 作者
- Xiang J、Liu Z、Liu M、Zhang Y、Zhu X
- 单位
- Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education), College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha 410081, China.China
- 文献类型
- 非美国政府资助研究
- 期刊
- Analytical chemistry2026 Feb 10
- 原文标识
- PubMed 41603436 · DOI 10.1021/acs.analchem.5c04471