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
离体表面修饰苯硼酸于 NK 细胞用于唾液酸介导的广谱癌细胞靶向
英文原题：Ex Vivo Surface Decoration of Phenylboronic Acid onto Natural Killer Cells for Sialic Acid-Mediated Versatile Cancer Cell Targeting.
查看英文原题
Ex Vivo Surface Decoration of Phenylboronic Acid onto Natural Killer Cells for Sialic Acid-Mediated Versatile Cancer Cell Targeting.
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中文摘要
苯硼酸（PBA）在唾液酸过表达的癌细胞中被高度认为是一种重要的癌症识别基团。在本研究中，脂质介导的生物材料将PBA分子整合到自然杀伤（NK）细胞表面，以构建受体介导的免疫细胞治疗模块。
因此，合成了1,2-二硬脂酰-sn-甘油-3-磷酸乙醇胺（DSPE）脂质偶联的二-PEG-PBA（DSPE PEG -di(PEG-PBA)）生物材料。DSPE PEG -di(PEG-PBA)生物材料对唾液酸（SA）表现出高亲和力，并通过pH 6.5和7.4下的荧光光谱得到证实。DSPE PEG -di(PEG-PBA)成功锚定在NK细胞表面（PBA-NK），该生物材料保持了固有特性，如活力、配体可用性（FasL和TRAIL）以及对LPS的细胞因子分泌反应。PBA-NK细胞的抗癌功效针对2D癌细胞（MDA-MB-231、HepG2和HCT-116）以及MDA-MB-231细胞的3D肿瘤球体进行了评估。PBA-NK细胞对SA过表达的癌细胞表现出显著增强的抗癌效果。
因此，PBA-NK细胞代表了一种用于癌症免疫治疗的新抗癌策略。
展开英文摘要原文
Phenylboronic acid (PBA) has been highly acknowledged as a significant cancer recognition moiety in sialic acid-overexpressing cancer cells. In this investigation, lipid-mediated biomaterial integrated PBA molecules onto the surface of natural killer (NK) cells to make a receptor-mediated immune cell therapeutic module.
Therefore, a 1,2-distearoyl- sn -glycero-3-phosphorylethanolamine (DSPE) lipid-conjugated di-PEG-PBA (DSPE PEG -di(PEG-PBA) biomaterial was synthesized. The DSPE PEG -di(PEG-PBA) biomaterial exhibited a high affinity for sialic acid (SA), confirmed by fluorescence spectroscopy at pH 6. 5 and 7. 4.
DSPE PEG -di(PEG-PBA) was successfully anchored onto NK cell surfaces (PBA-NK), and this biomaterial maintains intrinsic properties such as viability, ligand availability (FasL & TRAIL), and cytokine secretion response to LPS. The anticancer efficacy of PBA-NK cells was evaluated against 2D cancer cells (MDA-MB-231, HepG2, and HCT-116) and 3D tumor spheroids of MDA-MB-231 cells. PBA-NK cells exhibited greatly enhanced anticancer effects against SA-overexpressing cancer cells.
Thus, PBA-NK cells represent a new anticancer strategy for cancer immunotherapy.
论文信息
- 作者
- Jangid AK、Kim S、Park HW、Kim HJ、Kim K
- 单位
- Department of Chemical & Biochemical Engineering, College of Engineering, Dongguk University, Seoul 04620, South Korea.South Korea
- 文献类型
- 非美国政府资助研究
- 期刊
- Biomacromolecules2024 Jan 8
- 原文标识
- PubMed 38130077 · DOI 10.1021/acs.biomac.3c00916