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 journalArticle

29 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 languageEnglish
Pages (from-to)304-317
Number of pages14
JournalNature biomedical engineering
Volume2
Issue number5
DOIs
Publication statusPublished - 2018 May 1

Fingerprint

Tannins
Protein Transport
Peptides
Blood vessels
Proteins
Extracellular Matrix
Blood Vessels
Acids
Elastin
Myocardial Reperfusion Injury
Glycocalyx
Flavonoids
Myoblasts
Fibroblast Growth Factor 2
Fibroblasts
Drug Delivery Systems
Reperfusion Injury
Viruses
Collagen
Cardiac Output

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Computer Science Applications

Cite this

Shin, M., Lee, H. A., Lee, M., Shin, Y., Song, J. J., Kang, S. W., ... Lee, H. (2018). Targeting protein and peptide therapeutics to the heart via tannic acid modification. Nature biomedical engineering, 2(5), 304-317. https://doi.org/10.1038/s41551-018-0227-9
Shin, Mikyung ; Lee, Hyang Ae ; Lee, Mihyun ; Shin, Yoomi ; Song, Ji Joon ; Kang, Sun Woong ; Nam, Dae Hwan ; Jeon, Eun Je ; Cho, Mira ; Do, Minjae ; Park, Sunhyun ; Lee, Moon Sue ; Jang, Jae Hyung ; Cho, Seung Woo ; Kim, Ki Suk ; Lee, Haeshin. / Targeting protein and peptide therapeutics to the heart via tannic acid modification. In: Nature biomedical engineering. 2018 ; Vol. 2, No. 5. pp. 304-317.
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Shin, M, Lee, HA, Lee, M, Shin, Y, Song, JJ, Kang, SW, Nam, DH, Jeon, EJ, Cho, M, Do, M, Park, S, Lee, MS, Jang, JH, Cho, SW, Kim, KS & Lee, H 2018, 'Targeting protein and peptide therapeutics to the heart via tannic acid modification', Nature biomedical engineering, vol. 2, no. 5, pp. 304-317. https://doi.org/10.1038/s41551-018-0227-9

Targeting protein and peptide therapeutics to the heart via tannic acid modification. / Shin, Mikyung; Lee, Hyang Ae; Lee, Mihyun; Shin, Yoomi; Song, Ji Joon; Kang, Sun Woong; Nam, Dae Hwan; Jeon, Eun Je; Cho, Mira; Do, Minjae; Park, Sunhyun; Lee, Moon Sue; Jang, Jae Hyung; Cho, Seung Woo; Kim, Ki Suk; Lee, Haeshin.

In: Nature biomedical engineering, Vol. 2, No. 5, 01.05.2018, p. 304-317.

Research output: Contribution to journalArticle

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AU - Lee, Moon Sue

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AU - Lee, Haeshin

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