Fu Chen, Qin Jingcan, Liu Xinlong, Kong Fei
Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang 110122, China.
Department of Radiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, 600 Yi Shan Road, Shanghai 200233, China.
Pharmaceutics. 2022 Jun 21;14(7):1315. doi: 10.3390/pharmaceutics14071315.
The targeted delivery of drugs to tumor cells and prevention of premature release before reaching the target is one of the key challenges to developing nanomedicines. In this paper, galactose decorated trimethyl chitosan (GT)-camptothecin (CPT) prodrug nanoparticles (GT-ss-CPT NPs) were prepared from GT-CPT conjugates linked by dithiodipropionic acid. The obtained GT-ss-CPT NPs were spherical with a particle size of 184.1 nm. GT-ss-CPT NPs displayed low drug release under physiological conditions, whereas efficient drug release was triggered by high GSH concentration. GT-ss-CPT NPs exhibited a higher antitumor effect both in vitro and in vivo than the free drug counterpart. More importantly, GT-ss-CPT NPs reduced the high systematic toxicity of CPT to tumor-bearing mice. In summary, GT-ss-CPT NPs can not only inhibit the premature release of CPT but also have a great potential for targeted hepatocellular carcinoma chemotherapy.
将药物靶向递送至肿瘤细胞并防止其在到达靶点之前过早释放是开发纳米药物的关键挑战之一。本文中，由二硫代二丙酸连接的半乳糖修饰的三甲基壳聚糖（GT）-喜树碱（CPT）前药纳米颗粒（GT-ss-CPT NPs）由GT-CPT缀合物制备而成。所制备的GT-ss-CPT NPs呈球形，粒径为184.1 nm。GT-ss-CPT NPs在生理条件下药物释放较低，而高谷胱甘肽（GSH）浓度可触发高效的药物释放。GT-ss-CPT NPs在体外和体内均表现出比游离药物更高的抗肿瘤效果。更重要的是，GT-ss-CPT NPs降低了CPT对荷瘤小鼠的高全身毒性。总之，GT-ss-CPT NPs不仅可以抑制CPT的过早释放，而且在靶向肝细胞癌化疗方面具有巨大潜力。
