A polymer nanoparticle with engineered affinity for a vascular endothelial growth factor (VEGF165)

Hiroyuki Koide, Keiichi Yoshimatsu, Yu Hoshino, Shih Hui Lee, Ai Okajima, Saki Ariizumi, Yudai Narita, Yusuke Yonamine, Adam C. Weisman, Yuri Nishimura, Naoto Oku, Yoshiko Miura, Kenneth J. Shea

Research output: Contribution to journalArticlepeer-review

49 Citations (Scopus)

Abstract

Protein affinity reagents are widely used in basic research, diagnostics and separations and for clinical applications, the most common of which are antibodies. However, they often suffer from high cost, and difficulties in their development, production and storage. Here we show that a synthetic polymer nanoparticle (NP) can be engineered to have many of the functions of a protein affinity reagent. Polymer NPs with nM affinity to a key vascular endothelial growth factor (VEGF165) inhibit binding of the signalling protein to its receptor VEGFR-2, preventing receptor phosphorylation and downstream VEGF165-dependent endothelial cell migration and invasion into the extracellular matrix. In addition, the NPs inhibit VEGF-mediated new blood vessel formation in Matrigel plugs in vivo. Importantly, the non-toxic NPs were not found to exhibit off-target activity. These results support the assertion that synthetic polymers offer a new paradigm in the search for abiotic protein affinity reagents by providing many of the functions of their protein counterparts.

Original languageEnglish
Pages (from-to)715-722
Number of pages8
JournalNature Chemistry
Volume9
Issue number7
DOIs
Publication statusPublished - Jul 1 2017

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Chemical Engineering(all)

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