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PCN-223 as a Drug Carrier for Potential Treatment of Colorectal Cancer
Journal of Industrial and Engineering Chemistry ( IF 5.9 ) Pub Date : 2020-04-01 , DOI: 10.1016/j.jiec.2020.01.010
Nea Young Chun , Se-Na Kim , Youn Seo Choi , Young Bin Choy

Abstract Colorectal cancer is the second leading cause of cancer-related deaths worldwide. CRC is often treated with intravenous 5-fluorouracil (5FU). However, 5FU frequently shows low therapeutic efficacy and serious adverse events. Particulate drug carriers able to enhance intracellular delivery could be advantageous, since higher 5FU concentrations would be engulfed by cancer cells during a relatively short residence within the rectal space to improve local anti-cancer efficacy. Therefore, we propose a novel material based on a zirconium-based metal-organic framework (MOF), PCN-223, as a potential carrier of 5FU for rectal delivery of treatment for CRC. PCN-223 nanoparticles, prepared by the solvothermal method, exhibited a highly porous structure, whereby 79.4 μg/mg 5FU could be encapsulated and released in a sustained manner over 2 h in vitro. PCN-223 was internalized by the human colorectal cancer cell line, HCT-116, within 2 h, representing the period that rectally delivered particles reside within the rectum. Consequently, 5FU-loaded PCN-223 (5FU@PCN-223) treatment decreased the viability of HCT-116 cells compared with treatment with a bolus 5FU solution, suggesting improved drug efficacy over a short exposure time. Therefore, PCN-223 may be a promising carrier for rectal delivery of 5FU for treatment of colorectal cancer.

中文翻译:

PCN-223 作为潜在治疗结直肠癌的药物载体

摘要 结直肠癌是全球癌症相关死亡的第二大原因。CRC 通常用静脉注射 5-氟尿嘧啶 (5FU) 治疗。然而,5FU 经常表现出低疗效和严重的不良事件。能够增强细胞内递送的颗粒药物载体可能是有利的,因为更高浓度的 5FU 会在直肠空间内相对较短的停留期间被癌细胞吞噬,以提高局部抗癌功效。因此,我们提出了一种基于锆基金属有机框架 (MOF) 的新型材料 PCN-223,作为 5FU 的潜在载体,用于直肠治疗 CRC。通过溶剂热法制备的 PCN-223 纳米颗粒表现出高度多孔的结构,在体外 2 小时内可以包封并持续释放 79.4 μg/mg 5FU。PCN-223 在 2 小时内被人类结肠直肠癌细胞系 HCT-116 内化,这代表了直肠递送颗粒停留在直肠内的时期。因此,与使用推注 5FU 溶液处理相比,装载 5FU 的 PCN-223(5FU@PCN-223)处理降低了 HCT-116 细胞的活力,表明在短暴露时间内提高了药物功效。因此,PCN-223可能是直肠递送5FU治疗结直肠癌的有前景的载体。表明在较短的暴露时间内提高了药物疗效。因此,PCN-223可能是直肠递送5FU治疗结直肠癌的有前景的载体。表明在较短的暴露时间内提高了药物疗效。因此,PCN-223可能是直肠递送5FU治疗结直肠癌的有前景的载体。
更新日期:2020-04-01
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