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负载N-乙酰-L-半胱氨酸的非离子表面活性剂囊泡用于癌症治疗的体内研究。

Niosomes loading N-acetyl-L-cysteine for cancer treatment in vivo study.

作者信息

Mohamad Ebtesam A, Ali Abeer A, Sharaky Marwa, El-Gebaly Reem H

机构信息

Department of Biophysics, Faculty of Science, Cairo University, 12613, Giza, Egypt.

College of Applied Medical Sciences, Prince Sattam Bin Abdul-Aziz University, Al-Kharj, 11942, Kingdom of Saudi Arabia.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2024 Jun;397(6):4339-4353. doi: 10.1007/s00210-023-02893-9. Epub 2023 Dec 13.

Abstract

Scientists are seeking to find an effective treatment for tumors that has no side effects. N-Acetyl-l-cysteine (NAC) is a thiol compound extracted from garlic. Current study explores the potential of NAC-loaded niosomes (NAC-NIO) for tumor treatment in mice. NAC-loaded niosomes' efficiency, morphology, UV absorption, size distribution, zeta potential, release, and FTIR analysis were evaluated. For vivo study, 25 male BALB/c mice were divided to five groups: gp1 negative control (receive saline), gp2 positive control (tumor group), gp3 treated with NAC, gp4 treated with NAC-NIO at the same time of tumor injection, and gp5 treated with NAC-NIO after tumor growth (day 14). The impact of NAC-NIO on the tumor treatment was evaluated by measuring tumor size progress, comet assay, oxidative stress parameters (GSH, nitric oxide, MDA), western blot analysis, and histopathological investigation of tissues. NAC-NIO showed 72 ± 3% encapsulation efficiency and zeta potential - 5.95 mV with spherical shape. It was found that oral administration of NAC-NIO in a dose of 50 mg/kg provided significant protection against tumor cells. Our formulation decreases DNA injury significantly (P < 0.05). It was noticed that NAC-NIO can increase oxidative stress levels in tumor tissue. On the other hand, the caspase 3 and caspase 9 gene expression were upregulated significantly (P < 0.001) in mice administrated NAC-NIO compared with all other groups. Histological studies confirmed the protective effect of NAC-NIO against tumor especially for treatment during tumor growth protocol. The results suggested that oral delivery of NAC-NIO formulation improved antioxidant effect.

摘要

科学家们正在寻求找到一种对肿瘤有疗效且无副作用的治疗方法。N-乙酰-L-半胱氨酸(NAC)是一种从大蒜中提取的硫醇化合物。当前研究探索了负载NAC的脂质体(NAC-NIO)在小鼠肿瘤治疗中的潜力。评估了负载NAC的脂质体的效率、形态、紫外线吸收、尺寸分布、zeta电位、释放情况以及傅里叶变换红外光谱分析。对于体内研究,将25只雄性BALB/c小鼠分为五组:第1组为阴性对照组(接受生理盐水),第2组为阳性对照组(肿瘤组),第3组用NAC治疗,第4组在肿瘤注射时用NAC-NIO治疗,第5组在肿瘤生长后(第14天)用NAC-NIO治疗。通过测量肿瘤大小进展、彗星试验、氧化应激参数(谷胱甘肽、一氧化氮、丙二醛)、蛋白质免疫印迹分析以及组织的组织病理学研究来评估NAC-NIO对肿瘤治疗的影响。NAC-NIO显示出72±3%的包封率和-5.95 mV的zeta电位且呈球形。结果发现,以50 mg/kg的剂量口服NAC-NIO能为抵御肿瘤细胞提供显著保护。我们的制剂能显著降低DNA损伤(P<0.05)。注意到NAC-NIO可提高肿瘤组织中的氧化应激水平。另一方面,与所有其他组相比,给予NAC-NIO的小鼠中半胱天冬酶3和半胱天冬酶9基因表达显著上调(P<0.001)。组织学研究证实了NAC-NIO对肿瘤的保护作用,尤其是在肿瘤生长方案期间的治疗。结果表明,口服NAC-NIO制剂可提高抗氧化效果。

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