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细胞外囊泡增强了鸡血藤属化合物在慢性粒细胞白血病治疗中的抗肿瘤作用。

Extracellular vesicles enhance the antitumor effects of millettia species-derived compounds in chronic myelogenous leukemia therapy.

作者信息

Xie Zongzhou, Cheng Xiaozhen, Mao JianCang, Zhu Yingqi, Li Le, Mei Zhenxin

机构信息

Department of Oncology, Haikou City People's Hospital, Haikou, Hainan, China.

NHC (National Health Commission of the People's Republic of China) Key Laboratory of Tropical Disease Control, School of Tropical Medicine, Hainan Medical University, Haikou, Hainan, China.

出版信息

Front Chem. 2024 Jul 16;12:1425318. doi: 10.3389/fchem.2024.1425318. eCollection 2024.

Abstract

Several are being investigated as medicinal ingredients due to their promising anti-cancer and anti-inflammatory properties. However, the application of -derived compounds has been severely hindered by their poor aqueous solubility, rapid metabolism, and low bioavailability. Extracellular vesicles (EVs), which as membrane-bound phospholipid vesicle initiatively secreted through a variety of mammalian cells, are increasingly recognized as promising drug delivery vehicles. Therefore, EVs are with great potential to enhance both the stability and efficacy of the -derived compounds in treatment. In this study, extracellular vesicles derived from chronic myelogenous leukemia cells are developed for delivering the extracts of Champ and Drake-derived Homobutein. Notably, Homobutein-loaded EV (hEV) formed a stable and homogenous nanosized particle with high entrapment efficiency up to 55.7%. Moreover, EVs loaded with Homobutein were significantly more potent than free drugs in inhibiting K562 cell proliferation. The results demonstrated that intravenous injection of EV loaded with Homobutein effectively inhibits tumor growth in tumor-bearing mice compared to free Homobutein. Hence, this strategy can effectively enhance the efficacy of -derived drugs in chronic myelogenous leukemia therapy.

摘要

由于具有潜在的抗癌和抗炎特性,几种物质正在作为药用成分进行研究。然而,这些物质衍生的化合物由于其水溶性差、代谢快和生物利用度低,其应用受到严重阻碍。细胞外囊泡(EVs)作为通过多种哺乳动物细胞主动分泌的膜结合磷脂囊泡,越来越被认为是有前景的药物递送载体。因此,EVs在提高这些物质衍生化合物治疗的稳定性和疗效方面具有巨大潜力。在本研究中,开发了源自慢性粒细胞白血病细胞的细胞外囊泡,用于递送白屈菜提取物和地锦提取物衍生的高异黄酮。值得注意的是,负载高异黄酮的EV(hEV)形成了稳定且均匀的纳米级颗粒,包封率高达55.7%。此外,负载高异黄酮的EVs在抑制K562细胞增殖方面比游离药物显著更有效。结果表明,与游离高异黄酮相比,静脉注射负载高异黄酮的EV能有效抑制荷瘤小鼠的肿瘤生长。因此,该策略可有效提高这些物质衍生药物在慢性粒细胞白血病治疗中的疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35d5/11286385/c4680f95a7e1/fchem-12-1425318-g001.jpg

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