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Application of Periostin Peptide-Decorated Self-Assembled Protein Cage Nanoparticles for Therapeutic Angiogenesis
Ba Reun Kim1,2 (Postdoctoral Fellow), Jung Won Yoon1 (Graduate student), Hyukjun Choi3 (Graduate student), Dasol Kim1 (Reseacher), Sebyung Kang3 (Professor), Jae Ho Kim 1,4,* (Professor)
1Department of Physiology, Pusan National University School of Medicine,
2Department of Pharmacology, University of Texas Southwestern Medical Center,
3Department of Biological Sciences, Ulsan National Institute of Science and Technology,
4Research Institute of Convergence Biomedical Science and Technology, Pusan National University Yangsan Hospital
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, is known to stimulate the repair of ischemic tissues by promoting angiogenesis. We previously identified a novel angiogenic peptide (amino acids 142–151), which is responsible for the pro-angiogenic activity of periostin. To improve the in vivo delivery efficiency of periostin peptide, in the present study, we used proteins that self-assembled into hollow cage-like structures as a drug delivery nanoplatform. The periostin peptide was genetically inserted into lumazine synthase isolated from Aquifex aeolicus, consisting of 60 identical subunits having an icosahedral capsid architecture. The periostin peptide-bearing lumazine synthase protein cage nanoparticle, in which 60 periostin peptides were multivalently displayed, was expressed in Escherichia coli and purified to homogeneity. Next, we examined the angiogenic activities of the 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 the 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 PPs.
Abstract, Accepted Manuscript(in press) [Submitted on September 28, 2021, Accepted on November 10, 2021]
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