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Isolated cell-bound membrane vesicles (CBMVs) as a novel class of drug nanocarriers.
Journal of Nanobiotechnology ( IF 10.6 ) Pub Date : 2020-05-06 , DOI: 10.1186/s12951-020-00625-2
Yang Zhang 1, 2 , Yang Liu 1 , Wendiao Zhang 1 , Qisheng Tang 1 , Yun Zhou 1 , Yuanfang Li 1 , Tong Rong 1 , Huaying Wang 1 , Yong Chen 1
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BACKGROUND Cell-bound membrane vesicles (CBMVs) are a type of membrane vesicles different from the well-known extracellular vesicles (EVs). In recent years, the applications of EVs as drug delivery systems have been studied widely. A question may arise whether isolated CBMVs also have the possibility of being recruited as a drug delivery system or nanocarrier? METHODS To test the possibility, CBMVs were isolated/purified from the surfaces of cultured endothelial cells, loaded with a putative antitumor drug doxorubicin (Dox), and characterized. Subsequently, cellular experiments and animal experiments using mouse models were performed to determine the in vitro and in vivo antitumor effects of Dox-loaded CBMVs (Dox-CBMVs or Dox@CBMVs), respectively. RESULTS Both Dox-free and Dox-loaded CBMVs were globular-shaped and nanometer-sized with an average diameter of ~ 300-400 nm. Dox-CBMVs could be internalized by cells and could kill multiple types of cancer cells. The in vivo antitumor ability of Dox-CBMVs also was confirmed. Moreover, Quantifications of blood cells (white blood cells and platelets) and specific enzymes (aspartate aminotransferase and creatine kinase isoenzymes) showed that Dox-CBMVs had lower side effects compared with free Dox. CONCLUSIONS The data show that the CBMV-entrapped Doxorubicin has the antitumor efficacy with lower side effects. This study provides evidence supporting the possibility of isolated cell-bound membrane vesicles as a novel drug nanocarrier.

中文翻译:


分离的细胞结合膜囊泡(CBMV)作为一类新型药物纳米载体。



背景技术细胞结合膜囊泡(CBMV)是不同于众所周知的细胞外囊泡(EV)的膜囊泡类型。近年来,电动汽车作为药物输送系统的应用得到了广泛的研究。可能会出现一个问题:分离的 CBMV 是否也有可能被招募为药物输送系统或纳米载体?方法 为了测试这种可能性,从培养的内皮细胞表面分离/纯化 CBMV,负载假定的抗肿瘤药物阿霉素 (Dox),并进行表征。随后,利用小鼠模型进行细胞实验和动物实验,分别确定负载 Dox 的 CBMV(Dox-CBMVs 或 Dox@CBMVs)的体外和体内抗肿瘤作用。结果 不含 Dox 和负载 Dox 的 CBMV 均为球形和纳米尺寸,平均直径约为 300-400 nm。 Dox-CBMV 可以被细胞内化,并可以杀死多种类型的癌细胞。 Dox-CBMVs 的体内抗肿瘤能力也得到证实。此外,血细胞(白细胞和血小板)和特定酶(天冬氨酸转氨酶和肌酸激酶同工酶)的定量显示,与游离 Dox 相比,Dox-CBMV 的副作用较低。结论 数据表明,CBMV包埋的阿霉素具有抗肿瘤功效,且副作用较低。这项研究提供了证据支持分离的细胞结合膜囊泡作为新型药物纳米载体的可能性。
更新日期:2020-05-06
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