Mechanistic investigation into selective cytotoxic activities of gold nanoparticles functionalized with epidermal growth factor variants
Mechanistic investigation into selective cytotoxic activities of gold nanoparticles functionalized with epidermal growth factor variants
复制标题
DOI：
10.1007/s44211-022-00256-7
复制
发表时间：
2023-01-14
影响因子：
1.6
通讯作者：
Nakanishi，Jun
中科院分区：
文献类型：
--
作者：
Zhang，Aiwen;Abdellatef，Shimaa A. A.;Nakanishi，Jun
表皮生长因子（EGF）在与金纳米颗粒（GNP）结合后获得独特的选择性细胞毒性。我们以前已经开发了几种无赖氨酸的EGF突变体，用于纳米颗粒缀合物与EGF受体（EGFR）之间的有利相互作用，并发现一种突变体（SR：K28 S/K48 R）显示出更强的抗癌活性。然而，SR突变体中选择性细胞毒性增强的确切机制仍然没有解决。在这项研究中，我们分析了EGF变体的纳米颗粒缀合物如何与A431癌细胞在受体结合，激活和运输方面进行不同的相互作用。我们的研究结果表明，SR-GNP缀合物在细胞毒性增强中的基本特征是它们优先激活网格蛋白非依赖性内吞途径。这表明，我们不仅应该关注配体-受体结合亲和力，还应该关注受体内吞途径的选择性，以优化这种模式的抗癌效果。
Epidermal growth factor (EGF) gains unique selective cytotoxicity against cancer cells upon conjugation with gold nanoparticles (GNPs). We have previously developed several lysine-free EGF mutants for favorable interactions between the nanoparticle conjugates with EGF receptor (EGFR) and found one mutant (SR: K28S/K48R) showing stronger anticancer activities. However, the exact mechanisms for the selective cytotoxicity enhancement in the SR mutant remained unsolved. In this study, we analyzed how the nanoparticle conjugates of EGF variants interacted differently with A431 cancer cells, in terms of receptor binding, activation, and trafficking. Our results indicate that the essential feature of the SR-GNP conjugates in the cytotoxicity enhancement is their preferential activation of the clathrin-independent endocytosis pathway. It is suggested that we should focus on not only ligand-receptor binding affinity but also the selectivity of the receptor endocytic route to optimize the anticancer effects in this modality.Graphical abstract