Aptamer-functionalized mesenchymal stem cells-derived exosomes for targeted delivery of SN۳۸ to colon cancer cells

Objective(s): 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, SN۳۸ was entrapped into ADSCs-derived exosomes through the combination method of incubation, freeze-thaw, and surfactant treatment (SN۳۸/Exo). Then, SN۳۸/Exo was conjugated with anti-MUC۱ aptamer (SN۳۸/Exo-Apt), and its targeting ability and cytotoxicity towards cancer cells were investigated.Results: Encapsulation efficiency of SN۳۸ into exosomes (۵۸%) was significantly increased using our novel combination method. Furthermore, the in vitro results were indicative of the great cellular uptake of SN۳۸/Exo-Apt and its significant cytotoxicity on Mucin ۱ overexpressing cells (C۲۶ cancer cells) without noticeable cytotoxicity on normal cells (CHO cells). Conclusion: The results propose that our approach developed an efficient method for loading SN۳۸ as a hydrophobic drug into exosomes and decorating them with MUC۱ aptamer against Mucin ۱ overexpressing cells. So, SN۳۸/Exo-Apt could be considered a great platform in the future for the therapy of colorectal cancer.

Keywords:

Antineoplastic agents , Aptamer , Cancer , Extracellular vesicles , Mesenchymal stem cell