Evaluation of exosomes encapsulated recombinant Interleukin-29 for its in vitro anticancer studies

J Biotechnol. 2023 Aug 20:373:24-33. doi: 10.1016/j.jbiotec.2023.06.008. Epub 2023 Jun 30.

Abstract

Exosomes have recently been considered ideal biotherapeutic nanocarriers that broaden the frontiers of current drug delivery systems to overcome the shortcomings associated with cytokine-based immunotherapy. Using this approach, the current study aimed to assess anti-proliferative activity of purified IL-29 and exosomes encapsulated IL-29. The IL-29+pET-28a construct was transformed into Rosetta 2(DE3) cells which was used for the large-scale production of IL-29. Exosomes isolated from H1HeLa, and SF-767 cells using Total Exosome Isolation reagent were loaded with IL-29 via sonication. Isolation of exosomes was validated using their core protein signature by western blotting and specific miRNA profiles by RT-PCR. The drug loading efficiency of exosomes derived from H1HeLa cells was higher than that of SF-767-derived exosomes. The drug release kinetics of IL-29 encapsulated exosomes exhibited stable release of the recombinant drug. Around 50% of all cancer cell lines survived when IL-29 was administered at a concentration of 20 µg/mL. A survival rate of less than 10% was observed when cells were treated with 20 µg/mL IL-29 loaded exosomes. It was concluded that IL-29 loaded exosomes had a more significant cytotoxic effect against cancer cells, which might be attributed to sustained drug release, improved half-life, superior targeting efficacy, capacity to harness endogenous intracellular trafficking pathways, and heightened biocompatibility of exosomes.

Keywords: Cancer treatment; Exosomes; IL-29 encapsulated exosomes; Nanoparticles; Recombinant IL-29.

MeSH terms

  • Antineoplastic Agents* / metabolism
  • Antineoplastic Agents* / pharmacology
  • Cytokines / metabolism
  • Drug Delivery Systems
  • Exosomes* / metabolism
  • Immunologic Factors
  • Interleukins / genetics
  • Interleukins / metabolism
  • Interleukins / pharmacology

Substances

  • Antineoplastic Agents
  • Cytokines
  • Immunologic Factors
  • Interleukins