一种通过PI3K/AKT信号通路抗肾癌的新型草药提取物碳纳米点纳米药物

IF 3.9 3区 化学 Q2 CHEMISTRY, MULTIDISCIPLINARY RSC Advances Pub Date : 2024-11-14 DOI:10.1039/D4RA07181F
Ning Tian, Xiangling Liu, Xiaoyu He, Ying Liu, Lizhi Xiao, Penghui Wang, Di Zhang, Zhe Zhang, Yu Zhao, Quan Lin, Changkui Fu and Yingnan Jiang
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摘要

从一种草药提取物中制备出了具有窄尺寸分布、良好水溶性和高细胞膜渗透性的新型 Re 碳纳米点。它们对肾癌 A498 细胞和肾细胞癌具有很强的抑制作用。它们能刺激 A498 细胞产生 ROS、诱导线粒体功能障碍并加速细胞内钙离子的释放。对给药后的 A498 细胞进行了转录组学检测,并通过 qPCR 和免疫荧光分析了检测结果。结果表明,Re 碳纳米管能下调异常激活的 PI3K/AKT 信号通路,使细胞周期停滞在 S 期,同时抑制细胞增殖。最后,在线粒体功能异常的情况下,Re 纳米碳点最终可促进 A498 细胞凋亡。肿瘤小鼠体内实验进一步表明,Re 纳米碳点对异种移植肾癌肿瘤有很强的抑制作用。制备的 Re 碳纳米点具有良好的抗肾癌 A498 细胞和肾细胞癌的生物活性,有望成为一种低毒性、高安全性的治疗肾癌的潜在药物。
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A new herbal extract carbon nanodot nanomedicine for anti-renal cell carcinoma through the PI3K/AKT signaling pathway†

New Re carbon nanodots with narrow size distribution, good water solubility and high cell membrane permeability were prepared from a herbal extract. They exhibited high inhibitory effects on renal cancer A498 cells and renal cell carcinoma. They could stimulate the production of ROS, induce mitochondrial dysfunction, and accelerate the release of intracellular calcium ions in the A498 cells. Transcriptomic tests were performed on A498 cells after administration, and the results were analyzed by qPCR and immunofluorescence. The results suggested that the Re carbon nanodots could downregulate the abnormally activated PI3K/AKT signaling pathway and perform cell cycle arrest in the S phase along with the inhibition of cell proliferation. Finally, in conjunction with the abnormal mitochondrial function, the Re carbon nanodots could ultimately promote the apoptosis of the A498 cells. In vivo tumor-bearing mouse experiments further showed that the Re carbon nanodots had a strong inhibitory effect on xenograft kidney cancer tumors. The prepared Re carbon nanodots have good anti-renal cancer A498 cell and renal cell carcinoma bioactivity and are expected to be a potential drug for the treatment of kidney cancer with low toxicity and high safety.

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来源期刊
RSC Advances
RSC Advances chemical sciences-
CiteScore
7.50
自引率
2.60%
发文量
3116
审稿时长
1.6 months
期刊介绍: An international, peer-reviewed journal covering all of the chemical sciences, including multidisciplinary and emerging areas. RSC Advances is a gold open access journal allowing researchers free access to research articles, and offering an affordable open access publishing option for authors around the world.
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