Schematic showing the general synthesis of polymer nanoparticles and their chemical composition. Courtesy of Hiroyuki Koide and Kenneth Shea.Researchers have engineered a polymer nanoparticle that can switch off the signal that drives the growth of blood vessels in biological tissue [Koide et al., Nature Chemistry (2017), doi: 10.1038/nchem.2749].
The process of switching on and off biological responses is known as signal transduction and is controlled by specific signaling proteins that bind to receptor proteins in the membrane of cells. Regulating biological processes by interrupting signal transduction can be achieved using a protein affinity reagent, usually an antibody. Antibodies are widely applied in basic research, industrial processes, and medicine to isolate proteins or for analytical or diagnostic purposes but can be costly and difficult to develop, produce, and store.
Polymer nanoparticles, by contrast, are cheap and easy to make in large volumes and can be synthesized as protein affinity reagents with many of the functions of antibodies. Researchers from the Universities of California Irvine, Shizuoka, and Kyushu identified one such polymer nanoparticle from a small screen of potential candidates able to inhibit the signaling protein VEGF, which induces angiogenesis − the growth of blood vessels from surrounding tissue.
“Our synthetic organic polymer nanoparticle binds to the signaling protein, VEGF, blocking the biological response,” explains Kenneth J. Shea of the University of California Irvine. “The polymer nanoparticle, synthesized in a one-step polymerization reaction in water, can produce many of the functions of its antibody counterpart by inhibiting binding of the signaling protein VEGF to its receptor VEGFR.”
The non-biological (or abiotic) nanoparticles consist of crosslinked hydrogel organic copolymers of N-isopropyl acrylamide (NIPAm) with sulfated carbohydrate and hydrophobic monomers. The simple polymer nanoparticles can be produced rapidly in the chemistry lab. Crucially, the affinity of the nanoparticles for VEGF − which the team demonstrates both in vivo and in vitro − is based on the chemical composition and not the presence of ligands or antibodies with affinity to VEGF.
“Our results suggest the potential for lower cost alternatives to antibodies and establish the potential for using abiotic alternatives in many of the applications of more traditional protein affinity reagents,” says Shea.
There are, however, obstacles to overcome before the practicality of the approach can be established. Polymer nanoparticles must demonstrate efficacy comparable to antibodies for specific therapeutic applications, as well as the absence of toxicity or any ‘off target’ activity.
“We will be exploring the use of these nanoparticles in diagnostics and in applications that have proven to be challenging or unsuccessful for antibodies such as a broad spectrum anti-venom,” explains Shea.
This article was originally published in Nano Today (2017), doi: 10.1016/j.nantod.2017.04.003.