• Targeted delivery of SN38 to cancer cells with aptamer-functionalized exosomes
  • Elham Pishavar,1,* Rezvan Yazdian-Robati,2 Khalil Abnous,3 Maryam Hashemi,4 Seyed Mohammad Taghdisi,5 Zahra Salmasi,6
    1. Department of Translational Medicine, University of Ferrara, Italy
    2. Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
    3. Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
    4. Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
    5. Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
    6. Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran


  • Introduction: Exosomes are classified as a type of extracellular vesicles (EV) with a size of 30-150 nm which have important role in various situations such as signaling processes, antigen presentation, immunomodulatory functions, and tumor progression. Moreover, due to some advantages over other nano-carriers such as their natural origin, higher biocompatibility and longer circulation time, exosomes have been investigated a lot in delivery of drugs and other therapeutic agents. Exosomes have been isolated from various cell sources, as well as platelets, neutrophils, macrophages, and mesenchymal stem cells (MSCs). Many studies indicated that MSCs display some prominent benefits as an exosome source, including the higher yield of exosome production, lower immunogenicity, and more stability in human plasma. Recently, using aptamers has improved functionality of exosomes in biomedical applications including targeted drug delivery. 7-ethyl-10-hydroxycamptothecin (SN38) is an anticancer member of the camptothecin family with inhibitory effect on topoisomerase 1 and it can destroy the structure and function of DNA. One of the important limitations of SN38 is its instability in a physiological pH range due to its extremely low solubility in pharmaceutical media. In this study, exosomes derived from human adipocyte mesenchymal stem cells (ADSCs) were conjugated to the MUC1 aptamer (Exo-Apt) and then loaded with SN38 using our novel combination method. So, Exo-Apt could act as a suitable carrier for efficient delivery of hydrophobic drug (SN38) to cancer cells. Afterwards, the effect of targeted and non-targeted complexes on C26 and CHO cell lines were evaluated.
  • Methods: First, mesenchymal stem cells were isolated from human adipocyte tissue (prepared by liposuction) and characterized. Then, the exosomes were extracted by ultracentrifugation and covalently conjugated to the amine MUC1 aptamer (Exo-Apt). Afterwards, SN38 was loaded into Exo-Apt through the novel combination method of incubation, freeze-thaw, and surfactant treatment (SN38/Exo-Apt) and its targeting potential and cytotoxic effects on cancer cells were investigated.
  • Results: With our novel combination method, encapsulation efficiency of SN38 into exosomes was considerably enhanced (58%). Moreover, flow cytometry results revealed the great cellular uptake of SN38/Exo-Apt in C26 cancer cells. The remarkable cytotoxicity of SN38/Exo-Apt on C26 cells was exhibited without obvious toxicity on normal CHO cells through MTT assay.
  • Conclusion: Our results showed that SN38 as a hydrophobic drug was loaded efficiently into the Exo-Apt using our novel approach. Conjugation of exosome with MUC1 aptamer could enhanced the cellular uptake and significantly increased the cytotoxicity on C26 cells. So, SN38/Exo-Apt could be considered as a great platform for the therapy of colorectal cancer.
  • Keywords: Cancer, Exosomes, Human mesenchymal stem cells, Aptamer,, SN38