Department of Pharmacy, College of Pharmacy, The Catholic University of Korea, Bucheon 14662, Republic of Korea.
Departments of Polymer Science and Engineering & Materials Science and Engineering, Chungnam National University, Daejeon 34134, Republic of Korea.
Adv Drug Deliv Rev. 2024 Sep;212:115386. doi: 10.1016/j.addr.2024.115386. Epub 2024 Jul 4.
To maximize therapeutic effects and minimize unwanted effects, the interest in drug targeting to the endoplasmic reticulum (ER) or Golgi apparatus (GA) has been recently growing because two organelles are distributing hubs of cellular building/signaling components (e.g., proteins, lipids, Ca) to other organelles and the plasma membrane. Their structural or functional damages induce organelle stress (i.e., ER or GA stress), and their aggravation is strongly related to diseases (e.g., cancers, liver diseases, brain diseases). Many efforts have been developed to image (patho)physiological functions (e.g., oxidative stress, protein/lipid-related processing) and characteristics (e.g., pH, temperature, biothiols, reactive oxygen species) in the target organelles and to deliver drugs for organelle disruption using organelle-targeting moieties. Therefore, this review will overview the structure, (patho)physiological functions/characteristics, and related diseases of the organelles of interest. Future direction on ER or GA targeting will be discussed by understanding current strategies and investigations on targeting, imaging/sensing, and therapeutic systems.
为了最大限度地提高治疗效果,同时将不良反应最小化,人们对靶向内质网(ER)或高尔基体(GA)的药物产生了浓厚的兴趣,因为这两个细胞器是细胞构建/信号成分(如蛋白质、脂质、Ca)向其他细胞器和质膜分配的中心。它们的结构或功能损伤会导致细胞器应激(即 ER 或 GA 应激),其恶化与疾病(如癌症、肝病、脑病)密切相关。人们已经做出了许多努力来对目标细胞器中的(病理)生理功能(如氧化应激、蛋白质/脂质相关处理)和特征(如 pH 值、温度、生物硫醇、活性氧)进行成像,并使用细胞器靶向基团来递送用于细胞器破坏的药物。因此,本综述将概述这些细胞器的结构、(病理)生理功能/特征以及相关疾病。通过了解当前对靶向、成像/传感和治疗系统的研究,将讨论 ER 或 GA 靶向的未来方向。