Comparison of exosomes and ferritin protein nanocages for the delivery of membrane protein therapeutics

Eunji Cho, Gi Hoon Nam, Yeonsun Hong, Yoon Kyoung Kim, Dong Hwee Kim, Yoosoo Yang, In San Kim

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)

Abstract

Exosomes are small membrane vesicles secreted by most cell types that play an important role in intercellular communication. Due to the characteristic of transferring their biomacromolecules, exosomes have potential as a new alternative for delivering protein therapeutics. Here, we investigate whether exosomes provide crucial advantages over other nanoparticles, in particular protein nanocage formulations, as a delivery system for membrane protein therapeutics. We characterized membrane-scaffold–based exosomes and protein-scaffold–based ferritin nanocages, both harboring SIRPα (signal regulatory protein α), an antagonist of CD47 on tumor cells. The efficacy of these two systems in delivering protein therapeutics was compared by testing their ability to enhance phagocytosis of tumor cells by bone-marrow–derived macrophages and subsequent inhibition of in vivo tumor growth. These analyses allowed us to comprehensively conclude that the therapeutic index of exosome-mediated CD47 blockade against tumor growth inhibition was higher than that of the same dose of ferritin-SIRPα. The results of this analysis reveal the importance of the unique characteristics of exosomes, in particular their membrane scaffold, in improving therapeutic protein delivery compared with protein-scaffold–based nanocages.

Original languageEnglish
Pages (from-to)326-335
Number of pages10
JournalJournal of Controlled Release
Volume279
DOIs
Publication statusPublished - 2018 Jun 10

Keywords

  • CD47
  • Exosome
  • Ferritin nanocages
  • Membrane protein therapeutics
  • SIRPα

ASJC Scopus subject areas

  • Pharmaceutical Science

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