适配体功能化的间充质干细胞源外泌体,用于将SN38有针对性地传递给结肠癌细胞。
Aptamer-functionalized mesenchymal stem cells-derived exosomes for targeted delivery of SN38 to colon cancer cells.
发表日期:2023 Apr
作者:
Elham Pishavar, Rezvan Yazdian-Robati, Khalil Abnous, Maryam Hashemi, Mahboubeh Ebrahimian, Rozita Feizpour, Zahra Salmasi, Seyed Mohammad Taghdisi
来源:
Stem Cell Research & Therapy
摘要:
自然的纳米泡囊体——外泌体近年来引起越来越多的关注,作为生物相容性载体,可以为药物的输送提供适当的来源,从而提高药物的效力和安全性。本研究旨在从脂肪细胞组织(ADSCs)中分离出间充质干细胞,获得足够数量的外泌体进行药物输送。通过超速离心分离出外泌体后,在孵育、冻融和表面活性剂处理的组合方法下,将SN38包裹在ADSCs来源的外泌体中(SN38/Exo)。然后,将SN38/Exo与抗MUC1适配体结合(SN38/Exo-Apt),并研究其对癌细胞的靶向能力和细胞毒性。利用我们的新型组合方法,将SN38包裹在外泌体中的封装效率(58%)显著提高。此外,体外实验结果表明,SN38/Exo-Apt具有很好的细胞摄取和对黏液蛋白1高表达细胞(C26癌细胞)的显著细胞毒性,而对正常细胞(CHO细胞)的细胞毒性不明显。结果表明,我们的方法开发了一种有效将SN38作为疏水药物加载到外泌体中,并用MUC1适配体装饰其对黏液蛋白1高表达的癌细胞,因此,SN38/Exo-Apt在将来治疗结肠癌方面是一个很好的平台。
Known as natural nanovesicles, exosomes have attracted increased attention as biocompatible carriers throughout recent years, which can provide appropriate sources for incorporating and transferring drugs to desired cells in order to improve their effectiveness and safety.This study implicates the isolation of mesenchymal stem cells from adipocyte tissue (ADSCs) to acquire a proper amount of exosomes for drug delivery. As the exosomes were separated by ultracentrifugation, SN38 was entrapped into ADSCs-derived exosomes through the combination method of incubation, freeze-thaw, and surfactant treatment (SN38/Exo). Then, SN38/Exo was conjugated with anti-MUC1 aptamer (SN38/Exo-Apt), and its targeting ability and cytotoxicity towards cancer cells were investigated.Encapsulation efficiency of SN38 into exosomes (58%) was significantly increased using our novel combination method. Furthermore, the in vitro results were indicative of the great cellular uptake of SN38/Exo-Apt and its significant cytotoxicity on Mucin 1 overexpressing cells (C26 cancer cells) without noticeable cytotoxicity on normal cells (CHO cells).The results propose that our approach developed an efficient method for loading SN38 as a hydrophobic drug into exosomes and decorating them with MUC1 aptamer against Mucin 1 overexpressing cells. So, SN38/Exo-Apt could be considered a great platform in the future for the therapy of colorectal cancer.