BMB Reports

생화학분자생물학회 (Korean Society for Biochemistry and Molecular Biology)
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Application of periostin peptide-decorated self-assembled protein cage nanoparticles for therapeutic angiogenesis

  • Kim, Ba Reun (Department of Physiology, School of Medicine, Pusan National University) ;
  • Yoon, Jung Won (Department of Physiology, School of Medicine, Pusan National University) ;
  • Choi, Hyukjun (Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST)) ;
  • Kim, Dasol (Department of Physiology, School of Medicine, Pusan National University) ;
  • Kang, Sebyung (Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST)) ;
  • Kim, Jae Ho (Department of Physiology, School of Medicine, Pusan National University)
  • 투고 : 2021.09.28
  • 심사 : 2021.11.10
  • 발행 : 2022.04.30
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초록

Peptides are gaining substantial attention as therapeutics for human diseases. However, they have limitations such as low bioavailability and poor pharmacokinetics. Periostin, a matricellular protein, can stimulate the repair of ischemic tissues by promoting angiogenesis. We have previously reported that a novel angiogenic peptide (amino acids 142-151) is responsible for the pro-angiogenic activity of periostin. To improve the in vivo delivery efficiency of periostin peptide (PP), we used proteins self-assembled into a hollow cage-like structure as a drug delivery nanoplatform in the present study. The periostin peptide was genetically inserted into lumazine synthase (isolated from Aquifex aeolicus) consisting of 60 identical subunits with an icosahedral capsid architecture. The periostin peptide-bearing lumazine synthase protein cage nanoparticle with 60 periostin peptides multivalently displayed was expressed in Escherichia coli and purified to homogeneity. Next, we examined angiogenic activities of this periostin peptide-bearing lumazine synthase protein cage nanoparticle. AaLS-periostin peptide (AaLS-PP), but not AaLS, promoted migration, proliferation, and tube formation of human endothelial colony-forming cells in vitro. Intramuscular injection of PP and AaLS-PP increased blood perfusion and attenuated severe limb loss in the ischemic hindlimb. However, AaLS did not increase blood perfusion or alleviate tissue necrosis. Moreover, in vivo administration of AaLS-PP, but not AaLS, stimulated angiogenesis in the ischemic hindlimb. These results suggest that AaLS is a highly useful nanoplatform for delivering pro-angiogenic peptides such as PP.

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과제정보

This research was supported by the MRC programs (NRF-2015R1A5A2009656) of the National Research Foundation of Korea funded by the Ministry of Education, Science, and Technology (NRF-2020R1A2C2011654 and 2019R1A2C2002749).

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