Park, Hyun-Ji Kuai, Rui Jeon, Eun Je Seo, Yoojin Jung, Youngmee Moon, James J. Schwendeman, Anna Cho, Seung-Woo 2024-01-19T23:02:35Z 2024-01-19T23:02:35Z 2021-09-03 2018-04 0142-9612 https://pubs.kist.re.kr/handle/201004/121523 Therapeutic strategies using endogenous stem cell mobilizer can provide effective cell-free therapy for addressing various ischemic diseases. In particular, substance P (SP) exhibited therapeutic regeneration by facilitating mobilization of endogenous stem cells from bone marrow to the injured sites. However, its therapeutic effect has been limited due to short half-life and rapid degradation of administered SP peptides in vivo. Here we sought to develop high-density lipoprotein (HDL)-mimicking nanodiscs conjugated with SP (HDL-SP) in order to increase the in vivo half-life, bone marrow targeting, and therapeutic efficacy of SP for the treatment of diabetic peripheral ischemia. Conjugation of SP onto HDL nanodisc led to remarkable similar to 3215- and similar to 1060-fold increase in the ex vivo and in vivo half-lives of SP, respectively. Accordingly, HDL-SP nanodiscs improved retention of SP in bone marrow after systemic administration, leading to efficient mobilization of stem cells from bone marrow into blood circulation and reduction of systemic inflammation. Consequently, nanodisc based SP peptide delivery promoted blood vessel formation, blood perfusion recovery and markedly improved limb salvage in diabetic hindlimb ischemia model relative to administration of free SP without nanodisc modification. Therefore, HDL-SP nanodisc can provide a novel strategy for the treatment of diabetic ischemia and HDL nanodisc modification could be potentially useful for the extension of plasma circulation of other labile peptides. (C) 2018 Elsevier Ltd. All rights reserved. English ELSEVIER SCI LTD MESENCHYMAL STEM-CELLS SPINAL-CORD-INJURY SUBSTANCE-P HALF-LIFE NEUROKININ-1 RECEPTOR DRUG-DELIVERY SR-BI PROTEIN ATHEROSCLEROSIS PEGYLATION High-density lipoprotein-mimicking nanodiscs carrying peptide for enhanced therapeutic angiogenesis in diabetic hindlimb ischemia Article 10.1016/j.biomaterials.2018.01.027 1 BIOMATERIALS, v.161, pp.69 - 80 BIOMATERIALS 161 69 80 scie scopus 000427100300007 2-s2.0-85041463057 Engineering, Biomedical Materials Science, Biomaterials Engineering Materials Science Article MESENCHYMAL STEM-CELLS SPINAL-CORD-INJURY SUBSTANCE-P HALF-LIFE NEUROKININ-1 RECEPTOR DRUG-DELIVERY SR-BI PROTEIN ATHEROSCLEROSIS PEGYLATION Substance P High-density lipoprotein Stem cell mobilization Diabetic peripheral ischemia Therapeutic angiogenesis