Istanbul University, Istanbul Faculty of Medicine, Department of Physiology, Istanbul, Turkey.
Erciyes University, Education Faculty, Department of Sience Education, Kayseri, Turkey.
Toxicol In Vitro. 2022 Oct;84:105435. doi: 10.1016/j.tiv.2022.105435. Epub 2022 Jul 8.
In this study, as a new synthesis method, UV light was employed as a type of cross-linking agent to control drug storage and to produce nanoparticles of different sizes and to stabilize the nanoparticles for the first time. We showed that the exposure time of the 5FU albumin solution to UV light produces differences in the size and characterization of the nanoparticles and also produces different cytotoxic effects on MCF-7 breast cancer cells. While the 5FU-A1 nanoparticles we synthesized with 1 h UV storage were approximately 43 nm, the 5FU-A2 nanoparticles we synthesized with UV storage for 3 h increased to an average of 300 nm. 5FU-A1 (IC value: 2.5 μg/mL) was approximately 16 times more cytotoxic than free 5FU (IC value 39.39 μg/mL) on MCF-7 cancer cells. Moreover, when normal HUVEC cells are treated with 5FU-A1 at a concentration of 2.5 μg/mL, more than 80% of these normal cells remain viable. In addition, we examined the rate of early-to-late apoptosis and necrosis in MCF-7 cancer cells using the Annexin V/PI flow cytometry assay. According to our results, 5FU-A1 promoted the apoptosis pathway. Finally, we examined P-gp activity with MDR1/ABCB1 antibody by flow cytometry and Rhodamine123 with fluorescent dye.
在这项研究中，我们首次使用紫外光作为交联剂来控制药物储存并制备不同尺寸的纳米颗粒，这是一种新的合成方法。我们发现，5FU 白蛋白溶液暴露在紫外光下的时间会影响纳米颗粒的大小和性质，并且对 MCF-7 乳腺癌细胞产生不同的细胞毒性作用。当我们用 1 小时的紫外光储存来合成 5FU-A1 纳米颗粒时，其平均尺寸约为 43nm，而用 3 小时的紫外光储存来合成的 5FU-A2 纳米颗粒则增加到平均 300nm。与游离 5FU（IC 值为 39.39μg/mL）相比，5FU-A1（IC 值为 2.5μg/mL）对 MCF-7 癌细胞的细胞毒性约高 16 倍。此外，当用 2.5μg/mL 的浓度处理正常 HUVEC 细胞时，超过 80%的这些正常细胞仍然存活。此外，我们使用 Annexin V/PI 流式细胞术检测 MCF-7 癌细胞中的早晚期凋亡和坏死率。根据我们的结果，5FU-A1 促进了细胞凋亡途径。最后，我们使用 MDR1/ABCB1 抗体通过流式细胞术和荧光染料罗丹明 123 检测 P-gp 活性。
