Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraydah 52571, Saudi Arabia.
Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah 52571, Saudi Arabia.
Molecules. 2020 Nov 16;25(22):5336. doi: 10.3390/molecules25225336.
A proper execution of basic cellular functions requires well-controlled homeostasis including correct protein folding. Endoplasmic reticulum (ER) implements such functions by protein reshaping and post-translational modifications. Different insults imposed on cells could lead to ER stress-mediated signaling pathways, collectively called the unfolded protein response (UPR). ER stress is also closely linked with oxidative stress, which is a common feature of diseases such as stroke, neurodegeneration, inflammation, metabolic diseases, and cancer. The level of ER stress is higher in cancer cells, indicating that such cells are already struggling to survive. Prolonged ER stress in cancer cells is like an Achilles' heel, if aggravated by different agents including nanoparticles (NPs) may be exhausted off the pro-survival features and can be easily subjected to proapoptotic mode. Different types of NPs including silver, gold, silica, graphene, etc. have been used to augment the cytotoxicity by promoting ER stress-mediated cell death. The diverse physico-chemical properties of NPs play a great role in their biomedical applications. Some special NPs have been effectively used to address different types of cancers as these particles can be used as both toxicological or therapeutic agents. Several types of NPs, and anticancer drug nano-formulations have been engineered to target tumor cells to enhance their ER stress to promote their death. Therefore, mitigating ER stress in cancer cells in favor of cell death by ER-specific NPs is extremely important in future therapeutics and understanding the underlying mechanism of how cancer cells can respond to NP induced ER stress is a good choice for the development of novel therapeutics. Thus, in depth focus on NP-mediated ER stress will be helpful to boost up developing novel pro-drug candidates for triggering pro-death pathways in different cancers.
正确执行基本的细胞功能需要良好控制的内稳态，包括正确的蛋白质折叠。内质网 (ER) 通过蛋白质重塑和翻译后修饰来实现这些功能。施加在细胞上的不同刺激会导致内质网应激介导的信号通路，统称为未折叠蛋白反应 (UPR)。内质网应激也与氧化应激密切相关，氧化应激是中风、神经退行性疾病、炎症、代谢疾病和癌症等疾病的共同特征。癌细胞中的内质网应激水平较高，表明这些细胞已经在努力生存。癌细胞中的内质网应激持续时间较长，如果被包括纳米颗粒 (NPs) 在内的不同试剂加重，可能会耗尽其生存特征，并容易受到促凋亡模式的影响。不同类型的 NPs，包括银、金、硅、石墨烯等，已被用于通过促进内质网应激介导的细胞死亡来增强细胞毒性。NPs 的多样化物理化学性质在其生物医学应用中起着重要作用。一些特殊的 NPs 已被有效地用于治疗不同类型的癌症，因为这些颗粒可以用作毒性或治疗剂。已经设计了几种类型的 NPs 和抗癌药物纳米制剂来靶向肿瘤细胞，以增强其内质网应激，促进其死亡。因此，减轻癌细胞中的内质网应激以有利于内质网特异性 NPs 诱导的细胞死亡在未来的治疗和理解癌细胞如何对内质网应激的反应机制中非常重要，这是开发新型治疗方法的一个很好的选择。因此，深入关注 NP 介导的内质网应激将有助于开发新型前药候选物，以触发不同癌症中的促死亡途径。
