This study investigated the fabrication of gallic acid‐loaded chitosan nanoparticles (Gal‐Chi‐NPs) that enhanced the DNA damage and apoptotic features by inhibiting FEN‐1 expressions in MDA‐MB 231 cells. Gal‐Chi‐NPs were fabricated by the ionic gelation method, and it was characterized by several studies such as dynamic light spectroscopy, Fourier‐transforms infrared spectroscopy, x‐ray diffraction, scanning electron microscopy, energy‐dispersive x‐ray, atomic force microscopy, and thermogravimetric analysis. We have obtained that Gal‐Chi‐NPs displayed 182.2 nm with crystal, smooth surface, and heat stability in nature. Gal‐Chi‐NPs induce significant toxicity in MDA‐MB‐231 cells that compared with normal NIH‐3T3 cells. A significant reactive oxygen species (ROS) overproduction was observed in Gal‐Chi‐NPs treated MDA‐MB‐231. Flap endonuclease‐1 (FEN‐1) is a crucial protein involved in long patch base excision repair that is involved in repairing the chemotherapeutic mediated DNA‐damaged base. Therefore, inhibition of FEN‐1 protein expression is a crucial target for enhancing chemotherapeutical efficacy. In this study, we have obtained that Gal‐Chi‐NPs treatment enhanced the DNA damage by observing increased p‐H2AX, PARP1; and suppressed the expression of FEN‐1 in MDA‐MB‐231 cells. Moreover, Gal‐Chi‐NPs inhibited the expression of tumor proliferating markers p‐PI3K, AKT, cyclin‐D1, PCNA, and BCL‐2; induced proapoptotic proteins (Bax and caspase‐3) in MDA‐MB 231 cells. Thus, Gal‐Chi‐NPs induce DNA damage and apoptotic features and inhibit tumor proliferation by suppressing FEN‐1 expression in triple‐negative breast cancer cells.

中文翻译：

---

负载没食子酸的壳聚糖纳米粒子通过抑制三阴性乳腺癌细胞中的瓣状核酸内切酶-1来增强DNA损伤和细胞凋亡特征


本研究研究了没食子酸负载壳聚糖纳米颗粒 (Gal-Chi-NPs) 的制备，该纳米颗粒通过抑制 MDA-MB 231 细胞中的 FEN-1 表达来增强 DNA 损伤和凋亡特征。 Gal-Chi-NPs是通过离子凝胶法制备的，并通过动态光谱、傅里叶变换红外光谱、X射线衍射、扫描电子显微镜、能量色散X射线、原子力等多项研究对其进行了表征。显微镜和热重分析。我们发现 Gal-Chi-NPs 的波长为 182.2 nm，具有晶体、表面光滑和热稳定性。与正常 NIH-3T3 细胞相比，Gal-Chi-NPs 在 MDA-MB-231 细胞中诱导显着毒性。在 Gal-Chi-NPs 处理的 MDA-MB-231 中观察到显着的活性氧 (ROS) 过量产生。 Flap 核酸内切酶-1 (FEN-1) 是参与长补丁碱基切除修复的关键蛋白，参与修复化疗介导的 DNA 损伤碱基。因此，抑制FEN-1蛋白表达是增强化疗疗效的重要靶点。在这项研究中，我们通过观察 p-H2AX、PARP1 的增加，发现 Gal-Chi-NPs 治疗增强了 DNA 损伤；并抑制 MDA-MB-231 细胞中 FEN-1 的表达。此外，Gal-Chi-NPs 抑制肿瘤增殖标志物 p-PI3K、AKT、cyclin-D1、PCNA 和 BCL-2 的表达。在 MDA-MB 231 细胞中诱导促凋亡蛋白（Bax 和 caspase-3）。因此，Gal-Chi-NPs 诱导 DNA 损伤和细胞凋亡特征，并通过抑制三阴性乳腺癌细胞中 FEN-1 的表达来抑制肿瘤增殖。