研究动态
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通过靶向细胞内表位的分子印迹聚合物纳米颗粒调节 EGFR 活性。

Modulation of EGFR Activity by Molecularly Imprinted Polymer Nanoparticles Targeting Intracellular Epitopes.

发表日期:2023 Oct 30
作者: Stanislav S Piletsky, Ekaterina Baidyuk, Elena V Piletska, Larissa Lezina, Konstantin Shevchenko, Donald J L Jones, Thong H Cao, Rajinder Singh, Alan C Spivey, Eric O Aboagye, Sergey A Piletsky, Nickolai A Barlev
来源: Cellular & Molecular Immunology

摘要:

近年来,分子印迹聚合物纳米粒子(nanoMIP)已被证明是诊断和治疗应用中抗体的有吸引力的替代品。然而,仍然存在几个关键问题:细胞内表位作为 nanoMIP 结合的靶标有多合适?通过靶向特定表位可以在多大程度上调节蛋白质功能?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nanoMIP的模板,然后用于治疗具有不同EGFR表达水平的癌细胞。据观察,nanoMIP 印有来自 EGFR 胞内激酶结构域和胞外配体结合结构域的表位,导致细胞形成远离细胞表面的大 EGFR 病灶,导致自磷酸化减少,并对细胞活力产生影响。总的来说,这表明细胞内结构域靶向 nanoMIP 可以成为癌症治疗的潜在新工具。
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.