Tawfik Essam, Ahamed Maqusood, Almalik Abdulaziz, Alfaqeeh Mohammad, Alshamsan Aws
Nanomedicine Research Unit, Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; Life Science and Environment Research Institute, King Abdulaziz City of Science and Technology, Riyadh, Saudi Arabia.
King Abdullah Institute for Nanotechnology, King Saud University, Riyadh, Saudi Arabia.
Saudi Pharm J. 2017 Feb;25(2):206-213. doi: 10.1016/j.jsps.2016.05.010. Epub 2016 Jun 6.
In this study, we aimed to improve the anticancer effect of 5-FU on human colon cancer cell lines by incorporating in poly(d,l lactic--glycolic acid) (PLGA) nanoparticles (NPs). The 5-FU-PLGA NPs were prepared by nanoprecipitation technique. Prepared NPs were moderately dispersed with an average diameter of 133 ± 25.19 nm. Scanning Electron Microscope (SEM) images revealed spherical structures with subtle surface irregularity. Free 5-FU dose-response curves were constructed (12.5-2000 μM) using MTT assay on HCT 116 and HT-29 cell lines for 1, 3, and 5 days. The calculated IC on HCT 116 were 185 μM after 1 day, 11.3 μM after 3 days, and 1.48 μM after 5 days. On HT-29, IC was only reached after 5 days of 5-FU treatment (11.25 μM). The HCT 116 viability following treatment with 100 μM 5-FU in free or NPs forms for 3 days was 38.8% and 18.6%, respectively. Similarly, when 250 μM was applied, HCT 116 viability was 17.03% and 14.6% after treatment with free and NPs forms of 5-FU, respectively. Moreover, HT-29 cell viability after 250 μM 5-FU treatment in free or NPs forms was 55.45% and 34.01%, respectively. We also noticed that HCT 116 cells were more sensitive to 5-FU-PLGA NPs as compared to HT-29 cells. Overall, our data indicate that 5-FU activity is time dependent and the prolonged effects created by PLGA NPs may contribute, at least in part, to the noticed enhancement of the anticancer activity of 5-FU drug.
在本研究中，我们旨在通过将5-氟尿嘧啶（5-FU）包裹于聚（d，l-乳酸-乙醇酸）（PLGA）纳米颗粒（NPs）中来提高其对人结肠癌细胞系的抗癌效果。采用纳米沉淀技术制备了5-FU-PLGA NPs。制备的纳米颗粒分散适度，平均直径为133±25.19nm。扫描电子显微镜（SEM）图像显示为具有细微表面不规则的球形结构。使用MTT法在HCT 116和HT-29细胞系上构建了游离5-FU的剂量反应曲线（12.5 - 2000μM），作用时间为1、3和5天。HCT 116细胞在1天后的计算IC50为185μM，3天后为11.3μM，5天后为1.48μM。在HT-29细胞上，5-FU处理5天后才达到IC50（11.25μM）。用100μM游离或纳米颗粒形式的5-FU处理HCT 116细胞3天后，细胞活力分别为38.8%和18.6%。同样，当应用250μM时，游离和纳米颗粒形式的5-FU处理后，HCT 116细胞活力分别为17.03%和14.6%。此外，250μM游离或纳米颗粒形式的5-FU处理后，HT-29细胞活力分别为55.45%和34.01%。我们还注意到，与HT-29细胞相比，HCT 116细胞对5-FU-PLGA NPs更敏感。总体而言，我们的数据表明5-FU的活性具有时间依赖性，PLGA NPs产生的延长效应可能至少部分地促成了所观察到的5-FU药物抗癌活性的增强。
