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
英文原题:Carbon Quantum Dots-Based Nanozyme from Coffee Induces Cancer Cell Ferroptosis to Activate Antitumor Immunity.
Carbon Quantum Dots-Based Nanozyme from Coffee Induces Cancer Cell Ferroptosis to Activate Antitumor Immunity.
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碳量子点(CQDs)因其类酶特性相较于天然酶具有巨大潜力。因此,从自然资源尤其是日常食物中发现低毒性的基于CQDs的纳米酶,意味着探索人类疾病治疗策略的一个有前景的方向。在此,我们报道了一种基于CQDs的生物相容性纳米酶,其由绿原酸(ChA)制备而成,绿原酸是咖啡中一种主要的生物活性天然产物。我们发现ChA CQDs表现出明显的GSH氧化酶样活性,并随后通过干扰GPX4催化的脂质修复系统促进癌细胞铁死亡。在体内,ChA CQDs显著抑制了HepG2荷瘤小鼠的肿瘤生长,且副作用毒性可忽略不计。特别地,在肝癌H22荷瘤小鼠中,ChA CQDs招募了大量肿瘤浸润免疫细胞,包括T细胞、NK细胞和巨噬细胞,从而将“冷”肿瘤转化为“热”肿瘤以激活全身性抗肿瘤免疫应答。综上所述,我们的研究表明,来自咖啡的天然产物衍生CQDs可作为生物安全的纳米酶用于抗癌治疗,并可能有助于基于纳米技术的免疫治疗的发展。
Carbon quantum dots (CQDs) offer huge potential due to their enzymatic properties as compared to natural enzymes.
Thus, discovery of CQDs-based nanozymes with low toxicity from natural resources, especially daily food, implies a promising direction for exploring treatment strategies for human diseases.
Here, we report a CQDs-based biocompatible nanozyme prepared from chlorogenic acid (ChA), a major bioactive natural product from coffee.
We found that ChA CQDs exhibited obvious GSH oxidase-like activities and subsequently promoted cancer cell ferroptosis by perturbation of GPX4-catalyzed lipid repair systems. In vivo, ChA CQDs dramatically suppressed the tumor growth in HepG2-tumor-bearing mice with negligible side toxicity.
Particularly, in hepatoma H22-bearing mice, ChA CQDs recruited massive tumor-infiltrating immune cells including T cells, NK cells, and macrophages, thereby converting "cold" to "hot" tumors for activating systemic antitumor immune responses. Taken together, our study suggests that natural product-derived CQDs from coffee can serve as biologically safe nanozymes for anticancer therapeutics and may aid the development of nanotechnology-based immunotherapeutic.
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