Department of Chemistry, Imperial College London, Molecular Sciences Research Hub, White City Campus, London W12 0BZ, United Kingdom.
L.A. Orbeli Institute of Physiology NAS, Yerevan 0028, Republic of Armenia.
Nano Lett. 2023 Nov 8;23(21):9677-9682. doi: 10.1021/acs.nanolett.3c01374. Epub 2023 Oct 30.
In recent years, molecularly imprinted polymer nanoparticles (nanoMIPs) have proven to be an attractive alternative to antibodies in diagnostic and therapeutic applications. However, several key questions remain: how suitable are intracellular epitopes as targets for nanoMIP binding? And to what extent can protein function be modulated via targeting specific epitopes? To investigate this, three extracellular and three intracellular epitopes of epidermal growth factor receptor (EGFR) were used as templates for the synthesis of nanoMIPs which were then used to treat cancer cells with different expression levels of EGFR. It was observed that nanoMIPs imprinted with epitopes from the intracellular kinase domain and the extracellular ligand binding domain of EGFR caused cells to form large foci of EGFR sequestered away from the cell surface, caused a reduction in autophosphorylation, and demonstrated effects on cell viability. Collectively, this suggests that intracellular domain-targeting nanoMIPs can be a potential new tool for cancer therapy.
近年来，分子印迹聚合物纳米粒子（nanoMIPs）已被证明是诊断和治疗应用中抗体的一种有吸引力的替代品。然而，仍有几个关键问题需要解决：细胞内表位作为 nanoMIP 结合的靶标合适吗？通过靶向特定表位，蛋白质功能可以在多大程度上被调节？为了研究这一点，表皮生长因子受体（EGFR）的三个细胞外和三个细胞内表位被用作合成 nanoMIPs 的模板，然后用这些 nanoMIPs 来治疗 EGFR 表达水平不同的癌细胞。结果观察到，印迹有 EGFR 细胞内激酶结构域和细胞外配体结合结构域表位的 nanoMIPs 导致细胞形成远离细胞膜的大块 EGFR 隔离区，减少了自身磷酸化，并对细胞活力产生了影响。总的来说，这表明针对细胞内结构域的 nanoMIPs 可能成为癌症治疗的一种潜在新工具。
