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Surface modulation of extracellular vesicles with cell-penetrating peptide-conjugated lipids for improvement of intracellular delivery to endothelial cells

Huang, Tianwei (author)
Univ Tokyo, Sch Engn, Dept Bioengn, 7-3-1 Hongo,Bunkyo Ku, Tokyo 1138656, Japan.
Sato, Yuya (author)
Univ Tokyo, Sch Engn, Dept Bioengn, 7-3-1 Hongo,Bunkyo Ku, Tokyo 1138656, Japan.
Kuramochi, Akiko (author)
Natl Inst Adv Ind Sci & Technol, Cellular & Mol Biotechnol Res Inst CMB, AIST Tsukuba Cent 5,1-1-1 Higashi, Tsukuba, Ibaraki 3058565, Japan.
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Ohba, Yoshio (author)
Natl Inst Adv Ind Sci & Technol, Cellular & Mol Biotechnol Res Inst CMB, AIST Tsukuba Cent 5,1-1-1 Higashi, Tsukuba, Ibaraki 3058565, Japan.
Sano, Masayuki (author)
Natl Inst Adv Ind Sci & Technol, Cellular & Mol Biotechnol Res Inst CMB, AIST Tsukuba Cent 5,1-1-1 Higashi, Tsukuba, Ibaraki 3058565, Japan.
Miyagishi, Makoto (author)
Natl Inst Adv Ind Sci & Technol, Biomed Res Inst, AIST Tsukuba Cent 6,1-1-1 Higashi, Tsukuba, Ibaraki 3058565, Japan.
Tateno, Hiroaki (author)
Natl Inst Adv Ind Sci & Technol, Cellular & Mol Biotechnol Res Inst CMB, AIST Tsukuba Cent 5,1-1-1 Higashi, Tsukuba, Ibaraki 3058565, Japan.
Wadhwa, Renu (author)
Natl Inst Adv Ind Sci & Technol, AIST INDIA DAILAB, Cent 5-41, Tsukuba 3058565, Japan.;Univ Tsukuba, Sch Integrat & Global Majors SIGMA, Tsukuba Life Sci Innovat, Tsukuba 3058577, Japan.
Kawasaki, Kazunori (author)
Natl Inst Adv Ind Sci & Technol, Res Inst Electrochem Energy, Dept Energy & Environm, Mat Sci RG, 1-8-31 Midorigaoka, Ikeda, Osaka 5638577, Japan.
Uchida, Takeyuki (author)
Natl Inst Adv Ind Sci & Technol, Res Inst Electrochem Energy, Dept Energy & Environm, Mat Sci RG, 1-8-31 Midorigaoka, Ikeda, Osaka 5638577, Japan.
Nilsson Ekdahl, Kristina (author)
Uppsala universitet,Linnéuniversitetet,Institutionen för kemi och biomedicin (KOB),Uppsala University, Sweden,Linnaeus Ctr Biomat Chem, BMC,Vaskulärbiologi,Linnaeus Univ, Linnaeus Ctr Biomat Chem, SE-39182 Kalmar, Sweden.
Nilsson, Bo (author)
Uppsala universitet,Vaskulärbiologi
Chung, Ung-il (author)
Univ Tokyo, Sch Engn, Dept Bioengn, 7-3-1 Hongo,Bunkyo Ku, Tokyo 1138656, Japan.
Teramura, Yuji (author)
Uppsala universitet,Vaskulärbiologi,Natl Inst Adv Ind Sci & Technol, Cellular & Mol Biotechnol Res Inst CMB, AIST Tsukuba Cent 5,1-1-1 Higashi, Tsukuba, Ibaraki 3058565, Japan.;Univ Tsukuba, Masters Doctoral Program Life Sci Innovat T LSI, 1-1-1 Tennodai, Tsukuba, Ibaraki 3058577, Japan.
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Univ Tokyo, Sch Engn, Dept Bioengn, 7-3-1 Hongo,Bunkyo Ku, Tokyo 1138656, Japan Natl Inst Adv Ind Sci & Technol, Cellular & Mol Biotechnol Res Inst CMB, AIST Tsukuba Cent 5,1-1-1 Higashi, Tsukuba, Ibaraki 3058565, Japan. (creator_code:org_t)
Elsevier, 2023
2023
English.
In: Regenerative Therapy. - : Elsevier. - 2352-3204 .- 2352-3204. ; 22, s. 90-98
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Exosomes (diameter 30-200 nm) are a subtype of extracellular vesicles secreted by cells containing DNA, microRNA (miRNA), and proteins. Exosomes are expected to be valuable as a means of delivering drugs or functional miRNAs in treatment of diseases. However, the delivery of exosomes is not sufficiently effective, even though exosomes have intrinsic delivery functions. Cell-penetrating peptides (CPPs) are short peptide families that facilitate cellular intake of molecules and vesicles. We previously reported that the modification of cells, and liposomes with CPP-conjugated-lipids, CPPs conjugated with poly (ethylene glycol)-conjugated phospholipids (PEG-lipid), that induce adhesion by CPPs, can be useful for cell-based assays and harvesting liposomes. In this study, we aimed to modulate the exosome surface using Tat peptide (YGRKKRRQRRR)-PEG-lipids to improve intracellular delivery to endothelial cells. We isolated and characterized exosomes from the medium of HEK 293 T cell cultures. Tat conjugated PEG -lipids with different spacer molecular weights and lipid types were incorporated into exosomes using fluorescein isothiocyanate labeling to optimize the number of Tat-PEG-lipids immobilized on the exo-some surface. The exosomes modified with Tat-PEG-lipids were incubated with human umbilical vein endothelial cells (HUVECs) to study the interaction. Tat conjugated with 5 kDa PEG and C16 lipids incorporated on the exosome surface were highly detected inside HUVECs by flow cytometry. Fluores-cence was negligible in HUVECs for control groups. Thus, Tat-PEG-lipids can be modified on the exosome surface, improving the intracellular delivery of exosomes.(c) 2022, The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/ 4.0/).

Subject headings

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinsk bioteknologi -- Biomaterialvetenskap (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Medical Biotechnology -- Biomaterials Science (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Keyword

Extracellular vesicles
Exosome
Cell-penetrating peptide (CPP)
Tat peptide
Poly(ethylene glycol)-conjugated lipid (PEG-Lipid)
Biomedical Sciences
Biomedicinsk vetenskap

Publication and Content Type

ref (subject category)
art (subject category)

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