Universität zu Köln

Noguchi, Kosuke, Obuki, Momoko, Sumi, Haruka, Klussmann, Merlin, Morimoto, Kenta, Nakai, Shinya, Hashimoto, Takuya, Fujiwara, Daisuke, Fujii, Ikuo, Yuba, Eiji, Takatani-Nakase, Tomoka, Neundorf, Ines and Nakase, Ikuhiko (2021). Macropinocytosis-Inducible Extracellular Vesicles Modified with Antimicrobial Protein CAP18-Derived Cell-Penetrating Peptides for Efficient Intracellular Delivery. Mol. Pharm., 18 (9). S. 3290 - 3302. WASHINGTON: AMER CHEMICAL SOC. ISSN 1543-8392

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Abstract

The antimicrobial protein CAP18 (approximate molecular weight: 18 000), which was first isolated from rabbit granulocytes, comprises a C-terminal fragment that has negatively charged lipopolysaccharide binding activity. In this study, we found that CAP18 (106-121)-derived (sC18)(2) peptides have macropinocytosis-inducible biological functions. In addition, we found that these peptides are highly applicable for use as extracellular vesicle (exosomes, EV)-based intracellular delivery, which is expected to be a next-generation drug delivery carrier. Here, we demonstrate that dimerized (sC18)(2) peptides can be easily introduced on EV membranes when modified with a hydrophobic moiety, and that they show high potential for enhanced cellular uptake of EVs. By glycosaminoglycan-dependent induction of macropinocytosis, cellular EV uptake in targeted cells was strongly increased by the peptide modification made to EVs, and intriguingly, our herein presented technique is efficiently applicable for the cytosolic delivery of the biologically cell-killing functional toxin protein, saporin, which was artificially encapsulated in the EVs by electroporation, suggesting a useful technique for EV-based intracellular delivery of biofunctional molecules.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Noguchi, Kosuke UNSPECIFIED UNSPECIFIED UNSPECIFIED Obuki, Momoko UNSPECIFIED UNSPECIFIED UNSPECIFIED Sumi, Haruka UNSPECIFIED UNSPECIFIED UNSPECIFIED Klussmann, Merlin UNSPECIFIED UNSPECIFIED UNSPECIFIED Morimoto, Kenta UNSPECIFIED UNSPECIFIED UNSPECIFIED Nakai, Shinya UNSPECIFIED UNSPECIFIED UNSPECIFIED Hashimoto, Takuya UNSPECIFIED UNSPECIFIED UNSPECIFIED Fujiwara, Daisuke UNSPECIFIED UNSPECIFIED UNSPECIFIED Fujii, Ikuo UNSPECIFIED UNSPECIFIED UNSPECIFIED Yuba, Eiji UNSPECIFIED UNSPECIFIED UNSPECIFIED Takatani-Nakase, Tomoka UNSPECIFIED UNSPECIFIED UNSPECIFIED Neundorf, Ines UNSPECIFIED UNSPECIFIED UNSPECIFIED Nakase, Ikuhiko UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-581342
DOI:	10.1021/acs.molpharmaceut.1c00244
Journal or Publication Title:	Mol. Pharm.
Volume:	18
Number:	9
Page Range:	S. 3290 - 3302
Date:	2021
Publisher:	AMER CHEMICAL SOC
Place of Publication:	WASHINGTON
ISSN:	1543-8392
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ARGININE-RICH PEPTIDES; LIPOPOLYSACCHARIDE-BINDING PROTEIN; EXOSOMES; DOMAIN; CAP18; INTERNALIZATION; ACTIVATION; CONJUGATE; LEADS Multiple languages Medicine, Research & Experimental; Pharmacology & Pharmacy Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/58134