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作为一类新型药物纳米载体的分离的细胞结合膜囊泡（CBMVs）。

Isolated cell-bound membrane vesicles (CBMVs) as a novel class of drug nanocarriers.

机构信息

Jiangxi Key Laboratory for Microscale Interdisciplinary Study, Institute for Advanced Study, Nanchang University, 999 Xuefu Ave., Honggutan District, Nanchang, Jiangxi, 330031, People's Republic of China.

School of Materials Science and Engineering, Nanchang University, Nanchang, Jiangxi, 330031, People's Republic of China.

出版信息

J Nanobiotechnology. 2020 May 6;18(1):69. doi: 10.1186/s12951-020-00625-2.

DOI:10.1186/s12951-020-00625-2
PMID:32375799
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7204042/
Abstract

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.

摘要

背景

细胞结合膜囊泡（CBMVs）是一种不同于已知的细胞外囊泡（EVs）的膜囊泡。近年来，EVs 作为药物传递系统的应用已经得到了广泛的研究。人们可能会产生疑问，分离得到的 CBMVs 是否也有可能被招募为药物传递系统或纳米载体？

方法

为了验证这种可能性，从培养的内皮细胞表面分离/纯化 CBMVs，负载一种假定的抗肿瘤药物阿霉素（Dox），并对其进行表征。随后，通过使用小鼠模型进行细胞实验和动物实验，分别确定负载 Dox 的 CBMVs（Dox-CBMVs 或 Dox@CBMVs）的体外和体内抗肿瘤效果。

结果

无 Dox 和负载 Dox 的 CBMVs 均呈球形且纳米级大小，平均直径约为 300-400nm。Dox-CBMVs 可被细胞内化，并可杀死多种类型的癌细胞。体内抗肿瘤能力也得到了证实。此外，对血细胞（白细胞和血小板）和特定酶（天冬氨酸氨基转移酶和肌酸激酶同工酶）的定量分析表明，与游离 Dox 相比，Dox-CBMVs 的副作用更低。

结论

数据表明，CBMV 包裹的阿霉素具有抗肿瘤功效且副作用更低。本研究为分离的细胞结合膜囊泡作为新型药物纳米载体提供了证据支持。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8384/7204042/e22f257d5e2c/12951_2020_625_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8384/7204042/457ada26c616/12951_2020_625_Sch1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8384/7204042/8796ba7d82f3/12951_2020_625_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8384/7204042/ff2c18cee3de/12951_2020_625_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8384/7204042/7a73c8f62ae9/12951_2020_625_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8384/7204042/9b48d5cae21f/12951_2020_625_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8384/7204042/e4e92d21c777/12951_2020_625_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8384/7204042/3aede777825a/12951_2020_625_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8384/7204042/0326523158e4/12951_2020_625_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8384/7204042/78b1ca2a425d/12951_2020_625_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8384/7204042/365d9153fd3a/12951_2020_625_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8384/7204042/e22f257d5e2c/12951_2020_625_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8384/7204042/457ada26c616/12951_2020_625_Sch1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8384/7204042/8796ba7d82f3/12951_2020_625_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8384/7204042/ff2c18cee3de/12951_2020_625_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8384/7204042/7a73c8f62ae9/12951_2020_625_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8384/7204042/9b48d5cae21f/12951_2020_625_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8384/7204042/e4e92d21c777/12951_2020_625_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8384/7204042/3aede777825a/12951_2020_625_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8384/7204042/0326523158e4/12951_2020_625_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8384/7204042/78b1ca2a425d/12951_2020_625_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8384/7204042/365d9153fd3a/12951_2020_625_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8384/7204042/e22f257d5e2c/12951_2020_625_Fig10_HTML.jpg

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