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载奥沙利铂的聚合物核壳型 ZnO 纳米粒子的抗肿瘤前体作用在结直肠癌中的研究。

The advance anticancer role of polymeric core-shell ZnO nanoparticles containing oxaliplatin in colorectal cancer.

机构信息

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

Cancer Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

J Biochem Mol Toxicol. 2023 May;37(5):e23325. doi: 10.1002/jbt.23325. Epub 2023 Feb 27.

Abstract

We evaluated the activity of core-shell ZnO nanoparticles (ZnO-NPs@polymer shell) containing Oxaliplatin via polymerization through in vitro studies and in vivo mouse models of colorectal cancer. ZnO NPs were synthesized in situ when the polymerization step was completed by co-precipitation. Gadolinium coordinated-ZnONPs@polymer shell (ZnO-Gd NPs@polymer shell) was synthesized by exploiting Gd's oxophilicity (III). The biophysical properties of the NPs were studied using powder X-ray diffraction (PXRD), Fourier transforms infrared spectroscopy, Ultraviolet-visible spectroscopy (UV-Vis), field emission electron microscopy (FESEM), transmission electron microscopy (TEM), atomic force microscopy, dynamic light scattering, and z-potential. (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) was used to determine the antiproliferative activity of ZnO-Gd-OXA. Moreover, a xenograft mouse model of colon cancer was exerted to survey its antitumor activity and effect on tumor growth. In the following, the model was also evaluated by histological staining (H-E; Hematoxylin & Eosin and trichrome staining) and gene expression analyses through the application of RT-PCR/ELISA, which included biochemical evaluation (MDA, thiols, SOD, CAT). The formation of ZnO NPs, which contained a crystallite size of 16.8 nm, was confirmed by the outcomes of the PXRD analysis. The Plate-like morphology and presence of Pt were obtained in EDX outcomes. TEM analysis displayed the attained ZnO NPs in a spherical shape and a diameter of 33 ± 8.5 nm, while the hydrodynamic sizes indicated that the particles were highly aggregated. The biological results demonstrated that ZnO-Gd-OXA inhibited tumor growth by inducing reactive oxygen species and inhibiting fibrosis, warranting further research on this novel colorectal cancer treatment agent.

摘要

我们通过体外研究和结直肠癌小鼠模型评估了含有奥沙利铂的核壳 ZnO 纳米粒子(ZnO-NPs@聚合物壳)的活性。聚合完成时,通过共沉淀原位合成 ZnO 纳米粒子。利用 Gd 的亲氧性(III)合成了钆配位 ZnO-NPs@聚合物壳(ZnO-Gd NPs@聚合物壳)。通过粉末 X 射线衍射(PXRD)、傅里叶变换红外光谱、紫外可见光谱(UV-Vis)、场发射电子显微镜(FESEM)、透射电子显微镜(TEM)、原子力显微镜、动态光散射和 z 电位研究了 NPs 的生物物理性质。(3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴化物)(MTT)用于测定 ZnO-Gd-OXA 的抗增殖活性。此外,还对结肠癌异种移植小鼠模型进行了研究,以评估其抗肿瘤活性和对肿瘤生长的影响。接下来,还通过组织学染色(H-E;苏木精和伊红染色和三色染色)和 RT-PCR/ELISA 应用的基因表达分析评估了该模型,其中包括生化评估(MDA、巯基、SOD、CAT)。PXRD 分析结果证实形成了含有 16.8nm 晶粒度的 ZnO 纳米粒子。EDX 结果获得了板状形态和 Pt 的存在。TEM 分析显示获得的 ZnO NPs 呈球形,直径为 33±8.5nm,而水动力尺寸表明颗粒高度聚集。生物结果表明,ZnO-Gd-OXA 通过诱导活性氧物质和抑制纤维化抑制肿瘤生长,为这种新型结直肠癌治疗剂的进一步研究提供了依据。

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