Isolated cell-bound membrane vesicles (CBMVs) as a novel class of drug nanocarriers
Isolated cell-bound membrane vesicles (CBMVs) as a novel class of drug nanocarriers
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分离的细胞结合膜囊泡（CBMV）作为一类新型药物纳米载体
DOI：
10.1186/s12951-020-00625-2
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发表时间：
2020-05-06
影响因子：
10.2
通讯作者：
Chen Yong
中科院分区：
文献类型：
--
作者：
Zhang Yang;Liu Yang;Chen Yong
细胞结合膜囊泡（Cell-bindedmembranevesicles，CBMV）是一类不同于细胞外囊泡（extracellularvesicles，EV）的膜囊泡。近年来，电动汽车作为药物传递系统的应用得到了广泛的研究。可能会出现一个问题，即分离的CBMV是否也有可能被招募为药物递送系统或纳米载体？方法从培养的内皮细胞表面分离纯化CBMVs，负载抗肿瘤药物阿霉素（Dox），并对其进行鉴定。随后，使用小鼠模型进行细胞实验和动物实验以分别确定负载Dox的CBMV（Dox-CBMV或Dox@ CBMV）的体外和体内抗肿瘤作用。结果未加Dox和加Dox的CBMV均为球形，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-CBMV的体内抗肿瘤能力也得到了证实。此外，血细胞（白色血细胞和血小板）和特异性酶（天冬氨酸转氨酶和肌酸激酶同工酶）的定量显示Dox-CBMV与游离Dox相比具有更低的副作用。结论CBMV包埋阿霉素具有较好的抗肿瘤作用，且毒副作用小。本研究为分离的细胞结合膜囊泡作为新型药物纳米载体的可能性提供了证据。
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 similar to 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.