Development of a New Drug Delivery System from HELA-Derived Exosomes and the Effect of Docetaxel-Loaded Exosomes on Mitochondrial Apoptosis


Cenik M., Abas B. I. , Kocabiyik B., Demirbolat G. M. , Cevik O.

JOURNAL OF PHARMACEUTICAL INNOVATION, 2021 (Journal Indexed in SCI) identifier identifier

  • Publication Type: Article / Article
  • Publication Date: 2021
  • Doi Number: 10.1007/s12247-021-09566-1
  • Title of Journal : JOURNAL OF PHARMACEUTICAL INNOVATION
  • Keywords: Exosomes, HELA, Cervical cancer, Docetaxel, Apoptosis, CERVICAL-CANCER, PROSTATE-CANCER, VEHICLES, NANOCARRIERS, PACLITAXEL, BRAIN

Abstract

Purpose Exosomes have the potential to create new therapeutics as drug loading carriers. Their important inherent roles are stem from structures (also known natural liposomes) and strong biological stability in many cellular processes. The formation of a new drug delivery system in cervical cancer by loading a chemotherapeutic agent docetaxel into exosomes obtained from HELA cells is intended. Methods In this study, exosomes were isolated from HELA cells by ultracentrifugation method. Exosome membrane proteins CD9 and CD63 were analyzed by western blotting. Docetaxel was loaded into the exosomes by electroporation. Structures and sizes of docetaxel-loaded exosomes (Exo-Doc) were analyzed by scanning electron microscopy and dynamic light scattering technique. Cell viability with MTT assay and cell migration with scratch assay were measured. Apoptotic changes were measured by Annexin-V binding, Bax, Bcl-2, Caspase-3 protein, and gene expressions by western blotting and qPCR. Results It was observed that cell viability and cell migration were decreased, and Annexin-V binding increased after 1 mu g/mL Exo-Doc application to HELA cells by 24-h incubation. Bax and caspase-3 protein and gene expression were increased and Bcl-2 protein and gene expressions were decreased in cells. Exo-Doc induced mitochondrial apoptosis in HELA cells. Conclusion As a result, docetaxel-loaded HELA-derived exosome was generated as a new drug carrier and delivery system which was used to treat the cell itself with low doses of chemotherapeutic. Exo-Doc may be preferred for treating cervical patients in the clinic due to its low toxicity.