Novel alternatives to extracellular vesicle-based immunotherapy – exosome mimetics derived from natural killer cells

外体 微泡 体内 生物 癌症研究 细胞毒性 细胞毒性T细胞 体外 生物化学 基因 小RNA 生物技术
作者
Liya Zhu,Prakash Gangadaran,S Kalimuthu,Ji Min Oh,Se Hwan Baek,Shin Young Jeong,Sang‐Woo Lee,Jaetae Lee,Byeong‐Cheol Ahn
出处
期刊:Artificial Cells Nanomedicine and Biotechnology [Informa]
卷期号:46 (sup3): 166-179 被引量:96
标识
DOI:10.1080/21691401.2018.1489824
摘要

Exosomes are endogenous nanocarriers that can deliver biological information between cells. They are secreted by all cell types, including immune cells such as natural killer (NK) cells. However, mammalian cells release low quantities of exosomes, and the purification of exosomes is difficult. Here, nanovesicles were developed by extrusion of NK cells through filters with progressively smaller pore sizes to obtain exosome mimetics (NK-EM). The anti-tumour effect of the NK-EM was confirmed in vitro and in vivo. The morphological features of the NK-EM were revealed by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and Western blot. In vitro, the cytotoxicity of the NK-EM to cancer cells (glioblastoma, breast carcinoma, anaplastic thyroid cancer and hepatic carcinoma) was assessed using bioluminescence imaging (BLI) and CCK-8 assay. For in vivo study, a xenograft glioblastoma mouse model was established. The anti-tumour activity of NK-EM was confirmed in vivo by the significant decreases of BLI, size and weight (all p < .001) of the tumour compared with the control group. Moreover, NK-EM cytotoxicity for glioblastoma cells that related with decreased levels of the cell survival markers p-ERK and p-AKT, and increased levels of apoptosis protein markers cleaved-caspase 3, cytochrome-c and cleaved-PARP was confirmed. All those results suggest that NK-EM exert stronger killing effects to cancer cells compared with the traditional NK-Exo, at the same time, the tumour targeting ability of the NK-EM was obtained in vivo. Therefore, NK-EM might be a promising immunotherapeutic agent for treatment of cancer.
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