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 language | English |
|---|---|
| Pages (from-to) | 326-335 |
| Number of pages | 10 |
| Journal | Journal of Controlled Release |
| Volume | 279 |
| DOIs | |
| Publication status | Published - 2018 Jun 10 |
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Keywords
- CD47
- Exosome
- Ferritin nanocages
- Membrane protein therapeutics
- SIRPα
ASJC Scopus subject areas
- Pharmaceutical Science
Cite this
Comparison of exosomes and ferritin protein nanocages for the delivery of membrane protein therapeutics. / Cho, Eunji; Nam, Gi Hoon; Hong, Yeonsun; Kim, Yoon Kyoung; Kim, Dong-Hwee; Yang, Yoosoo; Kim, In-San.
In: Journal of Controlled Release, Vol. 279, 10.06.2018, p. 326-335.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Comparison of exosomes and ferritin protein nanocages for the delivery of membrane protein therapeutics
AU - Cho, Eunji
AU - Nam, Gi Hoon
AU - Hong, Yeonsun
AU - Kim, Yoon Kyoung
AU - Kim, Dong-Hwee
AU - Yang, Yoosoo
AU - Kim, In-San
PY - 2018/6/10
Y1 - 2018/6/10
N2 - 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.
AB - 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.
KW - CD47
KW - Exosome
KW - Ferritin nanocages
KW - Membrane protein therapeutics
KW - SIRPα
UR - http://www.scopus.com/inward/record.url?scp=85046358597&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85046358597&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2018.04.037
DO - 10.1016/j.jconrel.2018.04.037
M3 - Article
C2 - 29679665
AN - SCOPUS:85046358597
VL - 279
SP - 326
EP - 335
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
ER -