Targeting protein and peptide therapeutics to the heart via tannic acid modification

Mikyung Shin; Hyang Ae Lee; Mihyun Lee; Yoomi Shin; Ji Joon Song; Sun Woong Kang; Dae Hwan Nam; Eun Je Jeon; Mira Cho; Minjae Do; Sunhyun Park; Moon Sue Lee; Jae Hyung Jang; Seung Woo Cho; Ki Suk Kim; Haeshin Lee

doi:10.1038/s41551-018-0227-9

Targeting protein and peptide therapeutics to the heart via tannic acid modification

Mikyung Shin, Hyang Ae Lee, Mihyun Lee, Yoomi Shin, Ji Joon Song, Sun Woong Kang, Dae Hwan Nam, Eun Je Jeon, Mira Cho, Minjae Do, Sunhyun Park, Moon Sue Lee, Jae Hyung Jang, Seung Woo Cho, Ki Suk Kim, Haeshin Lee

Research output: Contribution to journal › Article › peer-review

148 Citations (Scopus)

Abstract

Systemic injection into blood vessels is the most common method of drug administration. However, targeting drugs to the heart is challenging, owing to its dynamic mechanical motions and large cardiac output. Here, we show that the modification of protein and peptide therapeutics with tannic acid - a flavonoid found in plants that adheres to extracellular matrices, elastins and collagens - improves their ability to specifically target heart tissue. Tannic-acid-modified (TANNylated) proteins do not adsorb on endothelial glycocalyx layers in blood vessels, yet they penetrate the endothelium to thermodynamically bind to myocardium extracellular matrix before being internalized by myoblasts. In a rat model of myocardial ischaemia-reperfusion injury, TANNylated basic fibroblast growth factor significantly reduced infarct size and increased cardiac function. TANNylation of systemically injected therapeutic proteins, peptides or viruses may enhance the treatment of heart diseases.

Original language	English
Pages (from-to)	304-317
Number of pages	14
Journal	Nature biomedical engineering
Volume	2
Issue number	5
DOIs	https://doi.org/10.1038/s41551-018-0227-9
Publication status	Published - 2018 May 1

Bibliographical note

Funding Information:
This work was supported by a grant from the National R&D Program for Cancer Control, Ministry for Health and Welfare, Republic of Korea (1631060 to H.L.). This work was also supported by a National Research Foundation of Korea (NRF) grant funded by the Ministry of Science, ICT and Future Planning for the following convergent research: a development programme for convergence research and development in traditional culture and current technology (NRF-2016M3C1B5906485 to H.L.), the Mid-career Researcher Program (NRF-2017R1A2A1A05001047 to H.L.) and the Basic Science Research Program funded by the Ministry of Education (NRF-2016R1A6A3A11933589 to M.S.). Further support was provided by the Technology Innovation Program (an establishment of risk management platform with the aim of reducing the attrition of new drugs and services) funded by the Ministry of Trade, Industry and Energy (10067737 (K.-S.K.)). The authors also thank B. S. Choi and H. N. Kim for advice on the ITC experiments.

Publisher Copyright:
© 2018 The Author(s) 2018, under exclusive licence to Macmillan Publishers Ltd, part of Springer Nature.

All Science Journal Classification (ASJC) codes

Biotechnology
Bioengineering
Medicine (miscellaneous)
Biomedical Engineering
Computer Science Applications

Access to Document

10.1038/s41551-018-0227-9

Cite this

@article{6cfed45f07884ec2b58d83f8e19100ec,

title = "Targeting protein and peptide therapeutics to the heart via tannic acid modification",

abstract = "Systemic injection into blood vessels is the most common method of drug administration. However, targeting drugs to the heart is challenging, owing to its dynamic mechanical motions and large cardiac output. Here, we show that the modification of protein and peptide therapeutics with tannic acid - a flavonoid found in plants that adheres to extracellular matrices, elastins and collagens - improves their ability to specifically target heart tissue. Tannic-acid-modified (TANNylated) proteins do not adsorb on endothelial glycocalyx layers in blood vessels, yet they penetrate the endothelium to thermodynamically bind to myocardium extracellular matrix before being internalized by myoblasts. In a rat model of myocardial ischaemia-reperfusion injury, TANNylated basic fibroblast growth factor significantly reduced infarct size and increased cardiac function. TANNylation of systemically injected therapeutic proteins, peptides or viruses may enhance the treatment of heart diseases.",

author = "Mikyung Shin and Lee, {Hyang Ae} and Mihyun Lee and Yoomi Shin and Song, {Ji Joon} and Kang, {Sun Woong} and Nam, {Dae Hwan} and Jeon, {Eun Je} and Mira Cho and Minjae Do and Sunhyun Park and Lee, {Moon Sue} and Jang, {Jae Hyung} and Cho, {Seung Woo} and Kim, {Ki Suk} and Haeshin Lee",

note = "Funding Information: This work was supported by a grant from the National R&D Program for Cancer Control, Ministry for Health and Welfare, Republic of Korea (1631060 to H.L.). This work was also supported by a National Research Foundation of Korea (NRF) grant funded by the Ministry of Science, ICT and Future Planning for the following convergent research: a development programme for convergence research and development in traditional culture and current technology (NRF-2016M3C1B5906485 to H.L.), the Mid-career Researcher Program (NRF-2017R1A2A1A05001047 to H.L.) and the Basic Science Research Program funded by the Ministry of Education (NRF-2016R1A6A3A11933589 to M.S.). Further support was provided by the Technology Innovation Program (an establishment of risk management platform with the aim of reducing the attrition of new drugs and services) funded by the Ministry of Trade, Industry and Energy (10067737 (K.-S.K.)). The authors also thank B. S. Choi and H. N. Kim for advice on the ITC experiments. Publisher Copyright: {\textcopyright} 2018 The Author(s) 2018, under exclusive licence to Macmillan Publishers Ltd, part of Springer Nature.",

year = "2018",

month = may,

day = "1",

doi = "10.1038/s41551-018-0227-9",

language = "English",

volume = "2",

pages = "304--317",

journal = "Nature Biomedical Engineering",

issn = "2157-846X",

publisher = "Nature Publishing Group",

number = "5",

}

TY - JOUR

T1 - Targeting protein and peptide therapeutics to the heart via tannic acid modification

AU - Shin, Mikyung

AU - Lee, Hyang Ae

AU - Lee, Mihyun

AU - Shin, Yoomi

AU - Song, Ji Joon

AU - Kang, Sun Woong

AU - Nam, Dae Hwan

AU - Jeon, Eun Je

AU - Cho, Mira

AU - Do, Minjae

AU - Park, Sunhyun

AU - Lee, Moon Sue

AU - Jang, Jae Hyung

AU - Cho, Seung Woo

AU - Kim, Ki Suk

AU - Lee, Haeshin

N1 - Funding Information: This work was supported by a grant from the National R&D Program for Cancer Control, Ministry for Health and Welfare, Republic of Korea (1631060 to H.L.). This work was also supported by a National Research Foundation of Korea (NRF) grant funded by the Ministry of Science, ICT and Future Planning for the following convergent research: a development programme for convergence research and development in traditional culture and current technology (NRF-2016M3C1B5906485 to H.L.), the Mid-career Researcher Program (NRF-2017R1A2A1A05001047 to H.L.) and the Basic Science Research Program funded by the Ministry of Education (NRF-2016R1A6A3A11933589 to M.S.). Further support was provided by the Technology Innovation Program (an establishment of risk management platform with the aim of reducing the attrition of new drugs and services) funded by the Ministry of Trade, Industry and Energy (10067737 (K.-S.K.)). The authors also thank B. S. Choi and H. N. Kim for advice on the ITC experiments. Publisher Copyright: © 2018 The Author(s) 2018, under exclusive licence to Macmillan Publishers Ltd, part of Springer Nature.

PY - 2018/5/1

Y1 - 2018/5/1

N2 - Systemic injection into blood vessels is the most common method of drug administration. However, targeting drugs to the heart is challenging, owing to its dynamic mechanical motions and large cardiac output. Here, we show that the modification of protein and peptide therapeutics with tannic acid - a flavonoid found in plants that adheres to extracellular matrices, elastins and collagens - improves their ability to specifically target heart tissue. Tannic-acid-modified (TANNylated) proteins do not adsorb on endothelial glycocalyx layers in blood vessels, yet they penetrate the endothelium to thermodynamically bind to myocardium extracellular matrix before being internalized by myoblasts. In a rat model of myocardial ischaemia-reperfusion injury, TANNylated basic fibroblast growth factor significantly reduced infarct size and increased cardiac function. TANNylation of systemically injected therapeutic proteins, peptides or viruses may enhance the treatment of heart diseases.

AB - Systemic injection into blood vessels is the most common method of drug administration. However, targeting drugs to the heart is challenging, owing to its dynamic mechanical motions and large cardiac output. Here, we show that the modification of protein and peptide therapeutics with tannic acid - a flavonoid found in plants that adheres to extracellular matrices, elastins and collagens - improves their ability to specifically target heart tissue. Tannic-acid-modified (TANNylated) proteins do not adsorb on endothelial glycocalyx layers in blood vessels, yet they penetrate the endothelium to thermodynamically bind to myocardium extracellular matrix before being internalized by myoblasts. In a rat model of myocardial ischaemia-reperfusion injury, TANNylated basic fibroblast growth factor significantly reduced infarct size and increased cardiac function. TANNylation of systemically injected therapeutic proteins, peptides or viruses may enhance the treatment of heart diseases.

UR - http://www.scopus.com/inward/record.url?scp=85046095113&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85046095113&partnerID=8YFLogxK

U2 - 10.1038/s41551-018-0227-9

DO - 10.1038/s41551-018-0227-9

M3 - Article

C2 - 30936449

AN - SCOPUS:85046095113

SN - 2157-846X

VL - 2

SP - 304

EP - 317

JO - Nature Biomedical Engineering

JF - Nature Biomedical Engineering

IS - 5

ER -

Targeting protein and peptide therapeutics to the heart via tannic acid modification

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this