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使用CREKA偶联纳米颗粒将胸腺素β4靶向递送至受损心肌。

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

作者信息

Huang Zheyong, Song Yanan, Pang Zhiqing, Zhang Bo, Yang Hongbo, Shi Hongtao, Chen Jing, Gong Hui, Qian Juying, Ge Junbo

机构信息

Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University.

School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai.

出版信息

Int J Nanomedicine. 2017 Apr 12;12:3023-3036. doi: 10.2147/IJN.S131949. eCollection 2017.

DOI:10.2147/IJN.S131949
PMID:28442910
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5396927/
Abstract

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.

摘要

目的

胸腺素β4（Tβ4）对心肌损伤具有多种有益作用，但其疗效受梗死灶内局部浓度低的限制。在此，我们基于梗死区内丰富的纤维蛋白与纤维蛋白靶向部分凝块结合肽半胱氨酸 - 精氨酸 - 谷氨酸 - 赖氨酸 - 丙氨酸（CREKA）之间的相互作用，建立了一种用于心脏修复的Tβ4递送系统。

方法与结果

将CREKA和Tβ4偶联到纳米颗粒上（CNP - Tβ4）。体外结合试验表明，与对照凝块（NP - Tβ4）相比，CNP - Tβ4对纤维蛋白凝块表面具有显著的结合能力。基于对缺血损伤早期纤维蛋白表达的验证，将CNP - Tβ4静脉注射给急性心肌缺血再灌注损伤的小鼠。CNP - Tβ4显示出比NP - Tβ4组更强的纤维蛋白靶向能力，主要积聚在梗死区域并与纤维蛋白共定位。随后，用CNP - Tβ4治疗产生了更好的治疗效果。

结论

CRKEA修饰有利于Tβ4在梗死区域的积聚和保留，从而增强功能效益。纤维蛋白靶向递送系统代表了一种可推广的再生医学平台技术。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2480/5396927/49b541e5e44a/ijn-12-3023Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2480/5396927/3738a532d0de/ijn-12-3023Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2480/5396927/70885ac7f412/ijn-12-3023Fig2.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2480/5396927/609fbb04f714/ijn-12-3023Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2480/5396927/988685053dce/ijn-12-3023Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2480/5396927/68eb18674822/ijn-12-3023Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2480/5396927/2dc4e942b612/ijn-12-3023Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2480/5396927/49b541e5e44a/ijn-12-3023Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2480/5396927/3738a532d0de/ijn-12-3023Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2480/5396927/70885ac7f412/ijn-12-3023Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2480/5396927/c9ae52c05123/ijn-12-3023Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2480/5396927/609fbb04f714/ijn-12-3023Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2480/5396927/988685053dce/ijn-12-3023Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2480/5396927/68eb18674822/ijn-12-3023Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2480/5396927/2dc4e942b612/ijn-12-3023Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2480/5396927/49b541e5e44a/ijn-12-3023Fig8.jpg

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