ATMP Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, 15179/64311, Iran.
Pathology Department, Dalhousie University, Halifax, B3H 4R2, Canada.
Nanomedicine (Lond). 2023 Feb;18(5):437-453. doi: 10.2217/nnm-2022-0237. Epub 2023 May 18.
We investigated the delivery of sorafenib (SFB) to breast cancer spheroids by natural killer cell-derived exosomes (NK-Exos). 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. 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. This is the first report for SFB loading into NK-Exos, which led to significant cytotoxic intensification against cancer cells.
我们研究了自然杀伤细胞衍生的外泌体（NK-Exos）向乳腺癌球体输送索拉非尼（SFB）的情况。 通过电穿孔构建 SFB-NK-Exos。 通过噻唑蓝（MTT）、吖啶橙/溴化乙锭（AO/EB）、4'，6-二脒基-2-苯基吲哚（DAPI）、膜联蛋白/碘化丙啶（Annexin/PI）、划痕和迁移实验、集落形成、逆转录聚合酶链反应（RT-PCR）、western blot 和脂噬试验评估其抗肿瘤作用。 负载效率为 46.66%。 SFB-NK-Exos 处理的球体显示出更高的细胞毒性作用（33%）和凋亡群体（44.9%）。 尽管 SFB-NK-Exos 制剂中的 SFB 浓度降低，但仍观察到与游离 SFB 相似的细胞毒性作用。 增加细胞内转运、药物持续释放和选择性抑制作用表明导航效率高。 这是首次将 SFB 载入 NK-Exos 的报道，这导致对癌细胞的显著细胞毒性增强。
