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使用 pH 敏感的藻酸盐@ZIF-8 纳米复合材料增强槲皮素的抗肿瘤和抗转移活性:研究。

Enhanced anti-tumor and anti-metastatic activity of quercetin using pH-sensitive Alginate@ZIF-8 nanocomposites:andstudy.

机构信息

Department of Pharmaceutical Biomaterials, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran.

Pharmaceutical Nanotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran.

出版信息

Nanotechnology. 2024 Sep 4;35(47). doi: 10.1088/1361-6528/ad713f.

DOI:10.1088/1361-6528/ad713f
PMID:39163872
Abstract

Quercetin (Qc) possesses anti-cancer properties, such as cell signaling, growth suppression, pro-apoptotic, anti-proliferative, and antioxidant effects. In this study, we developed an alginate-modified ZIF-8 (Alg@ZIF-8) to enhance the anti-tumor efficacy of Qc. The developed alginate-modified quercetin-loaded ZIF-8 (Alg@Qc@ZIF-8) was characterized using scanning electron microscope (SEM), dynamic light scattering (DLS), fourier transform infrared spectroscopy Thermogravimetric analysis, Brunauer-Emmett-Teller, and x-ray diffraction. The drug release pattern was evaluated at pH 5.4 and 7.4. The cytotoxicity of nanoparticles was assessed on the 4T1 cell line. Finally, the anti-tumor activity of Alg@Qc@ZIF-8 was evaluated in 4T1 tumor-bearing mice. SEM showed that the nanoparticles were spherical with a diameter of mainly below 50 nm. The DLS showed that the developed nanoparticles' hydrodynamic diameter, zeta potential, and polydispersity index were 154.9 ± 7.25 nm, -23.8 ± 5.33 mV, and 0.381 ± 0.09, respectively. The drug loading capacity was 10.40 ± 0.02%. Alg@Qc@ZIF-8 exhibited pH sensitivity, releasing more Qc at pH 5.4 (about 3.62 times) than at pH 7.4 after 24 h. Furthermore, the ICvalue of Alg@Qc@ZIF-8 on the 4T1 cell line was 2.16 times lower than net Qc. Importantly, in tumor-bearing mice, Alg@Qc@ZIF-8 demonstrated enhanced inhibitory effects on tumor growth and lung metastasis compared to net Qc. Considering theandoutcomes, Alg@Qc@ZIF-8 might hold great potential for effective breast cancer management.

摘要

槲皮素(Qc)具有抗癌特性,如细胞信号转导、生长抑制、促凋亡、抗增殖和抗氧化作用。在这项研究中,我们开发了一种海藻酸钠修饰的 ZIF-8(Alg@ZIF-8)来增强 Qc 的抗肿瘤功效。开发的海藻酸钠修饰的槲皮素负载 ZIF-8(Alg@Qc@ZIF-8)使用扫描电子显微镜(SEM)、动态光散射(DLS)、傅里叶变换红外光谱热重分析、Bru-nauer-Emmett-Teller 和 X 射线衍射进行了表征。在 pH 5.4 和 7.4 下评估了药物释放模式。纳米粒子的细胞毒性在 4T1 细胞系上进行了评估。最后,在 4T1 荷瘤小鼠中评估了 Alg@Qc@ZIF-8 的抗肿瘤活性。SEM 显示,纳米粒子呈球形,直径主要低于 50nm。DLS 显示,所开发的纳米粒子的水动力直径、Zeta 电位和多分散指数分别为 154.9±7.25nm、-23.8±5.33mV 和 0.381±0.09。药物载量为 10.40±0.02%。Alg@Qc@ZIF-8 表现出 pH 敏感性,在 pH 5.4 下(约 3.62 倍)比在 pH 7.4 下 24 小时后释放更多的 Qc。此外,Alg@Qc@ZIF-8 在 4T1 细胞系上的 IC50 值比 net Qc 低 2.16 倍。重要的是,在荷瘤小鼠中,与 net Qc 相比,Alg@Qc@ZIF-8 对肿瘤生长和肺转移具有更强的抑制作用。考虑到这些结果,Alg@Qc@ZIF-8 可能为有效治疗乳腺癌提供了巨大潜力。

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