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新型 NK 细胞来源外泌体递送索拉非尼增强三阴性乳腺癌凋亡

英文原题:Novel delivery of sorafenib by natural killer cell-derived exosomes-enhanced apoptosis in triple-negative breast cancer.

查看英文原题

Novel delivery of sorafenib by natural killer cell-derived exosomes-enhanced apoptosis in triple-negative breast cancer.

PubMed 2023/05/18(内容时间) Nanomedicine (Lond) Q2 · IF 4.6(JCR 2025)

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中文摘要

我们研究了通过NK 细胞来源的外泌体(NK-Exos)将索拉非尼(SFB)递送至乳腺癌球体。

通过电穿孔构建SFB-NK-Exos。通过甲基噻唑基四唑、吖啶橙/溴化乙锭、4',6-二脒基-2-苯基吲哚、膜联蛋白/碘化丙啶、划痕和迁移实验、集落形成、RT-PCR、western blot和脂噬实验评估其抗肿瘤效果。

载药效率为46.66%。SFB-NK-Exos处理的球体显示出更高的细胞毒性效应(33%)和凋亡群体(44.9%)。尽管SFB-NK-Exos制剂中SFB浓度降低,仍观察到与游离SFB相似的细胞毒性效应。增加的细胞内转运、药物的持续释放和选择性抑制作用证明了有效的导航。

这是首次将SFB负载到NK-Exos中的报告,这导致对癌细胞的细胞毒性显著增强。这个摘要关于什么?本研究描述了将一种称为索拉非尼(SFB)的抗癌药物递送至实验室培养的称为球体的球形癌细胞团。称为外泌体的碟形细胞结构被用作药物递送工具。这些外泌体由称为自然杀伤(NK)细胞的免疫细胞亚群产生。NK细胞负责杀死癌细胞。因此,这些外泌体与NK细胞具有相似的抗癌特性。我们想测试负载SFB的外泌体是否具有更好的抗癌效果。结果是什么?使用不同方法,SFB被负载在外泌体内并递送至球体。所获得的结果表明,外泌体与SFB的联合应用能够提高靶向效力,减少对正常细胞的副作用,并实现药物的持续释放。经此处理后,球体被以更高的效力杀灭。该研究结果意味着什么?NK细胞来源外泌体与SFB的联合应用可对癌细胞产生更好的细胞毒性。因此,与单用SFB治疗相比,该策略可能具有更好的抗癌效果。

展开英文摘要原文

Aim: We investigated the delivery of sorafenib (SFB) to breast cancer spheroids by natural killer cell-derived exosomes (NK-Exos). Methods: SFB-NK-Exos were constructed by electroporation. Their antitumor effects were evaluated by methyl thiazolyl tetrazolium, acridine orange/ethidium bromide, 4',6-diamidino-2-phenylindole, annexin/propidium iodide, scratch and migration assay, colony formation, RT-PCR, western blot and lipophagy tests. Result: The loading efficacy was 46. 66%.

SFB-NK-Exos-treated spheroids showed higher cytotoxic effects (33%) and apoptotic population (44. 9%). Despite the reduction of SFB concentration in the SFB-NK-Exos formulation, similar cytotoxic effects to those of free SFB were observed. Increased intracellular trafficking, sustained release of the drug and selective inhibitory effects demonstrated efficient navigation. Conclusion: This is the first report for SFB loading into NK-Exos, which led to significant cytotoxic intensification against cancer cells. What is this summary about?

This study describes the delivery of an anticancer drug called sorafenib (SFB) to laboratory-grown spherical masses of cancer cells called spheroids. Saucer-like cellular structures called exosomes were used as drug-delivery tools. These exosomes were produced by a subgroup of immune cells called natural killer (NK) cells. NK cells are responsible for killing cancer cells. So, these exosomes share similar anticancer properties with NK cells.

We wanted to test whether exosomes loaded with SFB would have better anticancer effects. What were the results? Using different methods, SFB was loaded within the exosomes and delivered to the spheroids. The obtained results showed that a combination of exosomes and SFB could improve the targeting efficacy, reducing the side effects to the normal cells and allowing continuous release of the drug.

The spheroids were killed with higher efficacy following this treatment. What do the results of the study mean? The combination of NK cell-derived exosomes and SFB could lead to better cytotoxicity against cancer cells.

Therefore, this strategy could have better anticancer effects compared with SFB treatment alone.

论文信息

作者
Hashemi ZS、Ghavami M、Kiaie SH、Mohammadi F、Barough MS、Khalili S、Hosseini-Farjam Z、Mossahebi-Mohammadi M
单位
ATMP Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, 15179/64311, Iran.Iran
期刊
Nanomedicine (London, England)2023 Feb
原文标识
PubMed 37199259 · DOI 10.2217/nnm-2022-0237