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

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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.
Publisher
NATURE PUBLISHING GROUP
Issue Date
2018-05
Language
English
Article Type
Article
Keywords

IN-VIVO DELIVERY; DRUG-DELIVERY; GENE DELIVERY; CELL DELIVERY; SOLID TUMORS; TISSUE; COLLAGEN; SIRNA; NANOPARTICLES; PROLONGATION

Citation

NATURE BIOMEDICAL ENGINEERING, v.2, no.5, pp.304 - 317

ISSN
2157-846X
DOI
10.1038/s41551-018-0227-9
URI
http://hdl.handle.net/10203/244324
Appears in Collection
BS-Journal Papers(저널논문)CH-Journal Papers(저널논문)
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