研究概要
结果表明,我们的方法建立了一种高效手段,可将疏水性药物 SN38 装载入外泌体,并用 MUC1 适配体修饰外泌体以靶向 Mucin 1 过表达的细胞。
中文摘要
目的:外泌体是天然纳米囊泡,近年来作为生物相容性载体受到关注,可将药物递送至目标细胞以提高疗效和安全性。方法:研究从脂肪组织分离间充质干细胞(ADSC),获取足量外泌体用于递药。超速离心分离外泌体后,采用孵育、冻融和表面活性剂处理相结合的新方法装载SN38,再偶联抗MUC1适配体,制得SN38/Exo-Apt,并评估靶向能力和细胞毒性。结果:新组合方法使SN38外泌体包封率提高至58%。体外实验显示,SN38/Exo-Apt可被细胞有效摄取,并对MUC1过表达的C26癌细胞产生显著细胞毒作用,而对正常CHO细胞未见明显毒性。结论:该方法可将疏水药物SN38高效装入外泌体,并以MUC1适配体修饰以靶向MUC1高表达细胞;该制剂有望成为结直肠癌治疗平台。
展开英文摘要原文
OBJECTIVES: 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.
MATERIALS AND METHODS: 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.
RESULTS: 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).
CONCLUSION: 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.
论文信息
- 作者
- Pishavar E、Yazdian-Robati R、Abnous K、Hashemi M、Ebrahimian M、Feizpour R、Salmasi Z、Taghdisi SM
- 第一作者单位
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.Iran
- 通讯作者单位
- Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.Iran
- 期刊
- Iranian journal of basic medical sciences2023 Apr