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载有 5-氟尿嘧啶的聚合物核壳 ZnO 纳米复合材料在提高结直肠癌抗癌活性方面的进展。

The advancing of polymeric core-shell ZnO nanocomposites containing 5-fluorouracil for improving anticancer activity in colorectal cancer.

机构信息

Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.

Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2024 Feb;397(2):899-911. doi: 10.1007/s00210-023-02643-x. Epub 2023 Aug 2.

Abstract

The study investigated the use of 5-fluorouracil-loaded ZnO nanocomposites (5-FU/Gd-ZnO NCs) as a potential treatment for cancer. 5-FU is a commonly used drug for cancer treatment but has undesirable side effects. The materials were characterized using various techniques, including PXRD, FTIR, FESEM, TEM, DLS, £-potential, and AFM. The data showed that the nanocomposites had a plate-like agglomeration with particle diameters ranging from 317.6 to 120.1 nm. The IC50 value of 5-FU-ZnO, which inhibits cell growth, was found to be 1.85 ppm. The effects of 5-FU-ZnO on inflammatory markers were also examined. While 5-FU increased the levels of TNF-a and IL-1b, the nanocomposites were able to reduce these levels. Additionally, the 5-FU/Gd-ZnO-NCs group showed an increase in thiol levels and a decrease in catalase and superoxide dismutase levels. Flow cytometry results showed that 5-FU, ZnO-NCs, and 5-FU/Gd-ZnO-NCs did not have any additive or synergistic effects on the suppression or eradication of cancer cells. In vivo, experiments showed that the 5-FU/Gd-ZnO NCs had similar necrotic characteristics and reduced fibrosis and collagen deposition compared to the free medication. The nanocomposites also exhibited higher antioxidative activity and lower inflammatory responses compared to the 5-FU group. It was shown that 5-FU/Gd-ZnO-NCs successfully inhibit cell proliferation. The in vivo results were comparable to those obtained with free 5-FU, suggesting the potential of these nanocomposites as therapeutic agents.

摘要

这项研究调查了负载 5-氟尿嘧啶的氧化锌纳米复合材料(5-FU/Gd-ZnO NCs)作为癌症治疗的潜在方法。5-氟尿嘧啶是一种常用于癌症治疗的药物,但具有不理想的副作用。该材料通过各种技术进行了表征,包括 PXRD、FTIR、FESEM、TEM、DLS、£-电位和 AFM。数据表明,纳米复合材料具有板状团聚,粒径范围为 317.6 至 120.1nm。抑制细胞生长的 5-FU-ZnO 的 IC50 值被发现为 1.85ppm。还检查了 5-FU-ZnO 对炎症标志物的影响。虽然 5-FU 增加了 TNF-a 和 IL-1b 的水平,但纳米复合材料能够降低这些水平。此外,5-FU/Gd-ZnO-NCs 组显示硫醇水平增加,过氧化氢酶和超氧化物歧化酶水平降低。流式细胞术结果表明,5-FU、ZnO-NCs 和 5-FU/Gd-ZnO-NCs 对抑制或消除癌细胞没有任何相加或协同作用。在体内实验中,结果表明 5-FU/Gd-ZnO NCs 具有与游离药物相似的坏死特征,并且与游离药物相比,纤维化和胶原蛋白沉积减少。与 5-FU 组相比,纳米复合材料还表现出更高的抗氧化活性和更低的炎症反应。结果表明,5-FU/Gd-ZnO-NCs 成功抑制了细胞增殖。体内结果与游离 5-FU 获得的结果相当,表明这些纳米复合材料作为治疗剂的潜力。

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