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Cardiac-specific delivery by cardiac tissue-targeting peptide-expressing exosomes

Authors
 Hyoeun Kim  ;  Nuri Yun  ;  Dasom Mun  ;  Ji-Young Kang  ;  Seung-Hyun Lee  ;  Hyelim Park  ;  Hyewon Park  ;  Boyoung Joung 
Citation
 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol.499(4) : 803-808, 2018-05 
Journal Title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
ISSN
 0006-291X 
Issue Date
2018-05
MeSH
Animals ; Drug Delivery Systems* ; Exosomes / drug effects ; Exosomes / metabolism* ; HEK293 Cells ; Humans ; Mice ; Myocardium / metabolism* ; Organ Specificity ; Peptides / pharmacology* ; Rats
Keywords
Cardiac-targeting peptide ; Exosome ; Specific-delivery
Abstract
Naturally occurring RNA carriers such as exosomes might be an untapped source of effective delivery vehicles. However, if exosomes are to be exploited for therapeutic applications, they must target specific tissues or cell types to avoid off-target effects. This study evaluated whether genetic modification of exosomes could enhance exosome delivery to heart cells and heart tissue without toxicity. Exosomes expressing cardiac-targeting peptide (CTP)-Lamp2b on the exosomal membrane (CTP-Exo) were generated by introducing vectors encoding CTP-Lamp2b into HEK 293 cells. The expression of CTP-Lamp2b peptide on exosomes was stabilized by attaching glycosylation sequences. Exosomes expressing only Lamp2b on exosomal membranes (CTL-Exo) were generated as a control. The in vitro and in vivo uptake of CTL-Exo and CTP-Exo was evaluated in cell lines and mice. Both exosomes were delivered to HEK 293 and H9C2 cells. The delivery of the exosome was not different between CTP-Exo and CTL-Exo in HEK 293 cells, whereas the delivery of CTP-Exo was 16% greater than that of CTL-Exo in H9C2 cells (P = 0.047). Cell viability was maintained at almost 100% with different dosages of both CTL-Exo and CTP-Exo. Moreover, compared with CTL-Exo, the in vivo delivery of exosomes to the hearts of mice was increased by 15% with CTP-Exo (P = 0.035). The delivery to livers and spleens was not different between the two exosomes. Genetic modification of exosomes by expressing CTP-Lamp2b on the exosomal membrane enhanced exosome delivery to heart cells and the heart tissue. These results suggested that CTP-Exo might be used as a therapeutic tool for heart disease.
Full Text
https://www.sciencedirect.com/science/article/pii/S0006291X18307605
DOI
10.1016/j.bbrc.2018.03.227
Appears in Collections:
6. Others (기타) > Dept. of Health Promotion (건강의학과) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Hyoeun(김효은) ORCID logo https://orcid.org/0000-0002-7334-9700
Park, Hye Lim(박혜림)
Lee, Seung Hyun(이승현) ORCID logo https://orcid.org/0000-0001-7549-9430
Joung, Bo Young(정보영) ORCID logo https://orcid.org/0000-0001-9036-7225
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/188893
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