PMID- 29746864 OWN - NLM STAT- MEDLINE DCOM- 20190513 LR - 20190513 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 501 IP - 3 DP - 2018 Jun 27 TI - Drug delivery using polyhistidine peptide-modified liposomes that target endogenous lysosome. PG - 648-653 LID - S0006-291X(18)31086-6 [pii] LID - 10.1016/j.bbrc.2018.05.037 [doi] AB - Cell-penetrating peptides (CPPs) can deliver payloads into cells by forming complexes with bioactive molecules via covalent or non-covalent bonds. Various CPPs have been applied in CPP-modified liposomes, and their effectiveness is highly regarded in liposomal drug delivery systems (DDSs). Previously, we have reported on the polyhistidine peptide (H16 peptide: HHHHHHHHHHHHHHHH-NH(2)) as a new CPP. The H16 peptide has a higher cell-penetrating capacity than well-known CPPs and delivers small molecules such as fluorescent dyes, bioactive peptides, and proteins into mammalian cells. However, it is not known whether the H16 peptide can deliver large cargos such as liposomes into cells. To assess the potential of the H16 peptide, in this study, we developed H16 peptide-modified liposomes (H16-Lipo) and evaluated their effectiveness in a liposomal DDS. The H16-Lipo was prepared by inserting a stearyl-H16 peptide into the hydrophobic region of a liposome. The H16-Lipo was internalized into human fibrosarcoma cells via multiple endocytosis pathways and localized to intracellular lysosomes. Based on this result, we used the H16-Lipo as a lysosome-targeting DDS. The H16-Lipo delivered alpha-galactosidase A (GLA), one of the lysosomal enzymes, to intracellular lysosomes and improved the proliferation of GLA-knockdown cells. These results suggest that the H16-Lipo is an effective drug carrier for lysosomal enzymes in a lysosome-targeting DDS. The loss of lysosomal enzymes has been known to induce metabolic disorders, called lysosomal storage diseases (LSDs). Our findings indicate that this combination of the H16 peptide and a liposome is a promising candidate as a DDS for the treatment of LSDs. CI - Copyright (c) 2018 Elsevier Inc. All rights reserved. FAU - Hayashi, Taiki AU - Hayashi T AD - Department of Agriculture, Graduate School of Sustainability Science, Tottori University, Tottori 680-8553, Japan. FAU - Shinagawa, Matsumi AU - Shinagawa M AD - Department of Bioresource Sciences, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan. FAU - Kawano, Tsuyoshi AU - Kawano T AD - Department of Agriculture, Graduate School of Sustainability Science, Tottori University, Tottori 680-8553, Japan; Department of Bioresource Sciences, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan. FAU - Iwasaki, Takashi AU - Iwasaki T AD - Department of Agriculture, Graduate School of Sustainability Science, Tottori University, Tottori 680-8553, Japan; Department of Bioresource Sciences, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan. Electronic address: itaka@tottori-u.ac.jp. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Liposomes) RN - 26062-48-6 (polyhistidine) RN - 4QD397987E (Histidine) RN - EC 3.2.1.22 (alpha-Galactosidase) SB - IM MH - Cell Line, Tumor MH - Drug Delivery Systems MH - Histidine/chemistry/*metabolism MH - Humans MH - Liposomes/chemistry/*metabolism MH - Lysosomes/*metabolism MH - alpha-Galactosidase/*administration & dosage/pharmacokinetics OTO - NOTNLM OT - Cell-penetrating peptide OT - Drug delivery system OT - Histidine OT - Liposome OT - Lysosome EDAT- 2018/05/11 06:00 MHDA- 2019/05/14 06:00 CRDT- 2018/05/11 06:00 PHST- 2018/04/26 00:00 [received] PHST- 2018/05/06 00:00 [accepted] PHST- 2018/05/11 06:00 [pubmed] PHST- 2019/05/14 06:00 [medline] PHST- 2018/05/11 06:00 [entrez] AID - S0006-291X(18)31086-6 [pii] AID - 10.1016/j.bbrc.2018.05.037 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2018 Jun 27;501(3):648-653. doi: 10.1016/j.bbrc.2018.05.037.