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

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 f...

Full description

Saved in:
Bibliographic Details
Published inNature biomedical engineering Vol. 2; no. 5; pp. 304 - 317
Main Authors 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
Format Journal Article
LanguageEnglish
Published England Nature Publishing Group 01.05.2018
Subjects
Acids
Animals
Blood vessels
Cardiac output
Cardiotonic Agents - chemistry
Cardiotonic Agents - pharmacology
Cardiotonic Agents - therapeutic use
Collagen
Coronary artery disease
Disease Models, Animal
Drug delivery
Drug Delivery Systems
Endothelium
Extracellular matrix
Fibroblast growth factor 2
Fibroblast Growth Factors
Flavonoids
Growth factors
Heart
Heart - drug effects
Heart diseases
Injury prevention
Ischemia
Male
Mice, Inbred BALB C
Myoblasts
Myocardial Reperfusion Injury - drug therapy
Myocardial Reperfusion Injury - pathology
Myocardium
Peptides
Proteins
Rats
Rats, Sprague-Dawley
Reperfusion
Tannic acid
Tannins - chemistry
Tannins - pharmacology
Tannins - therapeutic use
Online AccessGet full text

Cover

More Information
Summary: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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:2157-846X
2157-846X
DOI:10.1038/s41551-018-0227-9