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适体功能化间充质干细胞衍生的外泌体用于将SN38靶向递送至结肠癌细胞。

Aptamer-functionalized mesenchymal stem cells-derived exosomes for targeted delivery of SN38 to colon cancer cells.

作者信息

Pishavar Elham, Yazdian-Robati Rezvan, Abnous Khalil, Hashemi Maryam, Ebrahimian Mahboubeh, Feizpour Rozita, Salmasi Zahra, Taghdisi Seyed Mohammad

机构信息

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Department of Translational Medicine, University of Ferrara, Italy.

出版信息

Iran J Basic Med Sci. 2023 Apr;26(4):388-394. doi: 10.22038/IJBMS.2023.68039.14873.

Abstract

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.

摘要

目的

外泌体作为天然纳米囊泡,近年来作为生物相容性载体受到越来越多的关注,它可为将药物包裹并转运至目标细胞提供合适的来源,以提高药物的有效性和安全性。

材料与方法

本研究涉及从脂肪组织中分离间充质干细胞(ADSCs),以获取适量用于药物递送的外泌体。通过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方法将SN38包封到ADSCs来源的外泌体中(SN38/Exo)。然后,将SN38/Exo与抗MUC1适配体偶联(SN38/Exo-Apt),并研究其对癌细胞的靶向能力和细胞毒性。

结果

使用我们的新型组合方法,SN38在外泌体中的包封效率(58%)显著提高。此外,体外结果表明SN38/Exo-Apt具有良好的细胞摄取能力,对过表达粘蛋白1的细胞(C26癌细胞)具有显著的细胞毒性,而对正常细胞(CHO细胞)无明显细胞毒性。

结论

结果表明,我们的方法开发了一种将疏水性药物SN38装载到外泌体中并使用抗MUC1适配体修饰以靶向过表达粘蛋白1细胞的有效方法。因此,SN38/Exo-Apt未来可被视为治疗结直肠癌的良好平台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/484b/10008394/cfbfbc0fae12/IJBMS-26-388-g001.jpg

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