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

83 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

Bibliographical note

Funding Information:
This work was supported by grants from the National Research Foundation of Korea (NRF) funded by the Korean Government (2017R1A2B2010292 and 2017R1A3B1023418), the KU-KIST Graduate School of Converging Science and Technology Program, and the KIST Institutional Program.

Funding Information:
This work was supported by grants from the National Research Foundation of Korea (NRF) funded by the Korean Government ( 2017R1A2B2010292 and 2017R1A3B1023418 ), the KU-KIST Graduate School of Converging Science and Technology Program , and the KIST Institutional Program . Appendix A

Publisher Copyright:
© 2018 Elsevier B.V.

Keywords

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

ASJC Scopus subject areas

  • Pharmaceutical Science

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