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Targeted delivery of thymosin beta 4 to the injured myocardium using CREKA-conjugated nanoparticles

Authors Huang Z, Song Y, Pang Z, Zhang B, Yang H, Shi H, Chen J, Gong H, Qian J, Ge J

Received 8 January 2017

Accepted for publication 2 March 2017

Published 12 April 2017 Volume 2017:12 Pages 3023—3036

DOI https://doi.org/10.2147/IJN.S131949

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Linlin Sun


Zheyong Huang,1,* Yanan Song,1,* Zhiqing Pang,2 Bo Zhang,3 Hongbo Yang,1 Hongtao Shi,1 Jing Chen,1 Hui Gong,1,4 Juying Qian,1 Junbo Ge1,4

1Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 2School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai, 3Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, 4Institute of Biomedical Science, Fudan University, Shanghai, People’s Republic of China

*These authors contributed equally to this work

Purpose: Thymosin beta 4 (Tβ4) has multiple beneficial facets for myocardial injury, but its efficiency is limited by the low local concentration within the infarct. Here, we established a Tβ4 delivery system for cardiac repair based on the interaction between the abundant fibrin in the infarct zone and the fibrin-targeting moiety clot-binding peptide cysteine–arginine–glutamic acid–lysine–alanine (CREKA).
Methods and results:
CREKA and Tβ4 were conjugated to nanoparticles (CNP–Tβ4). In vitro binding test revealed that CNP–Tβ4 had a significant binding ability to the surface of fibrin clots when compared to the control clots (NP–Tβ4). Based on the validation of fibrin expression in the early stage of ischemia injury, CNP–Tβ4 was intravenously administered to mice with acute myocardial ischemia–reperfusion injury. CNP–Tβ4 revealed a stronger fibrin-targeting ability than the NP–Tβ4 group and accumulated mainly in the infarcted area and colocalized with fibrin. Subsequently, treatment with CNP–Tβ4 resulted in a better therapeutic effect.
Conclusion: CRKEA modification favored Tβ4 accumulation and retention in the infarcted region, leading to augmented functional benefits. Fibrin-targeting delivery system represents a generalizable platform technology for regenerative medicine.

Keywords:
thymosin beta 4, fibrin, CREKA, targeting delivery, ischemia reperfusion, cardiovascular

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