Department of Medical Laboratory Science and Biotechnology, College of Medical Technology, Chung Hwa University of Medical Technology, Tainan, Taiwan; Department of Surgery, China Medical University Beigang Hospital, Beigang, Yunlin, Taiwan.
Department of Food Nutrition and Health Biotechnology, Asia University, Taichung, Taiwan.
Toxicol Appl Pharmacol. 2019 Nov 1;382:114734. doi: 10.1016/j.taap.2019.114734. Epub 2019 Aug 27.
Curcumin (Cur), a natural product, has been shown to have anti-tumor activities in many human cancer cells. Gefitinib (Gef) is a clinical drug for cancer patients. However, there is no available information to show whether Gef/Cur nanoparticles (NPs) increased cell apoptosis and anti-tumor effects on xenograft mice model in vivo. In this study, γ-polyglutamic acid-coated nanoparticles loaded with Gef and Cur (γ-PGA-Gef/Cur NPs) were developed and its physicochemical properties and antitumor effects were investigated in vitro and in vivo. The γ-PGA-Gef/Cur NPs showed 548.5 ± 93.7 nm in diameter and -40.3 ± 3.87 mV on surface charge. The loading efficiencies of Gef and Cur were 89.5 and 100%, respectively. γ-PGA-Gef/Cur NPs could be internalized into SAS cells and significantly decreased total cell viability of SAS cells. Western blotting results indicated that both free Gef/Cur and γ-PGA-Gef/Cur NPs induced apoptotic cell death via caspase- and mitochondria-dependent pathways. In vivo studies indicated that treatments of PLGA NPs, free Gef/Cur, and γ-PGA-Gef/Cur NPs did not significantly affect appearances and bodyweights of mice. But the γ-PGA-Gef/Cur NPs significantly suppressed tumor size when comparing to free Gef/Cur-treated group. The nanoparticles developed in this study may be used as a potential therapy for oral cancer.
姜黄素（Cur）是一种天然产物，已在许多人类癌细胞中显示出抗肿瘤活性。吉非替尼（Gef）是一种癌症患者的临床药物。然而，没有可用的信息表明 Gef/Cur 纳米颗粒（NPs）是否在体内异种移植小鼠模型中增加细胞凋亡和抗肿瘤作用。在这项研究中，开发了 γ-聚谷氨酸（γ-PGA）包裹的载有 Gef 和 Cur 的纳米颗粒（γ-PGA-Gef/Cur NPs），并在体外和体内研究了其理化性质和抗肿瘤作用。γ-PGA-Gef/Cur NPs 的直径为 548.5±93.7nm，表面电荷为-40.3±3.87mV。Gef 和 Cur 的载药效率分别为 89.5%和 100%。γ-PGA-Gef/Cur NPs 可以被 SAS 细胞内化，并显著降低 SAS 细胞的总细胞活力。Western blot 结果表明，游离 Gef/Cur 和 γ-PGA-Gef/Cur NPs 均可通过 caspase 和线粒体依赖性途径诱导细胞凋亡。体内研究表明，PLGA NPs、游离 Gef/Cur 和 γ-PGA-Gef/Cur NPs 处理均未显著影响小鼠的外观和体重。但与游离 Gef/Cur 处理组相比，γ-PGA-Gef/Cur NPs 显著抑制了肿瘤大小。本研究开发的纳米颗粒可作为口腔癌的潜在治疗方法。
