Department of Medical Biochemistry, Graduate Division of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, Shizuoka 422-8526, Japan.
Department of Chemistry, University of California Irvine, Irvine, California 92697, USA.
Nat Chem. 2017 Jul;9(7):715-722. doi: 10.1038/nchem.2749. Epub 2017 Mar 27.
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 (VEGF) inhibit binding of the signalling protein to its receptor VEGFR-2, preventing receptor phosphorylation and downstream VEGF-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.
蛋白质亲和试剂广泛应用于基础研究、诊断和分离以及临床应用，其中最常见的是抗体。然而，它们通常存在成本高、开发、生产和储存困难等问题。在这里，我们展示了一种合成聚合物纳米粒子（NP）可以被设计具有许多蛋白质亲和试剂的功能。对关键的血管内皮生长因子（VEGF）具有纳摩尔亲和力的聚合物 NP 可抑制信号蛋白与其受体 VEGFR-2 的结合，阻止受体磷酸化以及下游 VEGF 依赖性内皮细胞迁移和侵入细胞外基质。此外，NP 还可抑制体内 Matrigel 塞中 VEGF 介导的新血管形成。重要的是，未发现无毒的 NP 具有脱靶活性。这些结果支持了这样一种观点，即合成聚合物通过提供许多与其蛋白质对应物相同的功能，为寻找非生物蛋白质亲和试剂提供了新的范例。
