期刊
JOURNAL OF CONTROLLED RELEASE
卷 279, 期 -, 页码 326-335出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2018.04.037
关键词
Exosome; Membrane protein therapeutics; Ferritin nanocages; SIRP alpha; CD47
资金
- National Research Foundation of Korea (NRF) - Korean Government [2017R1A2B2010292, 2017R1A3B1023418]
- KU-KIST Graduate School of Converging Science and Technology Program
- KIST Institutional Program
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 SIRP alpha (signal regulatory protein alpha), 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-SIRP alpha. 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.
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