Sayed Fatma Al-Zahraa, Mohamed Ayman S, Fahmy Heba Mohamed
Biophysics, Badr University in Cairo, 15 Fair Zone - 4th floor-Nasr City - Cairo - Egypt, Badr, 11829, EGYPT.
Zoology, Faculty of Science , Cairo University, Giza, Egypt, Giza, 12613, EGYPT.
Nanotechnology. 2024 Oct 2. doi: 10.1088/1361-6528/ad823f.
Doxorubicin is one of the most common wide-spectrum chemotherapeutics. However, its efficacy is limited due to off-target accumulation and selectivity issues. In this study, we compared the anti-cancer effect and biocompatibility of KaoliniteMeOH-Dox, a doxorubicin repackaging, to doxorubicin monotherapy. The formulation was extensively tested using transmission electron microscopy, dynamic light scattering, zeta potential, Fourier transform infrared, x-ray diffraction, and in vitro drug release. The MTT assay measured MCF-7 cell growth inhibition in vitro. In vivo testing involved 20 naïve mice and 40 Ehrlich solid tumor-inoculated mice. The tumor size was monitored for 18 days. In all experimental groups, tumor and cardiac tissues were evaluated for cytotoxicity and genotoxicity by addressing oxidative stress, histopathology, and comet assay. We found that kaoliniteMeOH-Dox has many advantages in terms of size, charge, shape, high loading efficiency (90.16%), and pH-dependent release. The MTT assay showed that the formulation outperformed doxorubicin in growth inhibition and selectivity. In vivo, research showed that kaoliniteMeOH-Dox suppressed tumors by 86.075% compared to 60.379% for free doxorubicin. Histological analysis showed that kaoliniteMeOH-Dox reduced tumor size, metastasis, and carcinogenic oxidative stress and inflammation in mice without harming naive mice. Based on the obtained data, the kaoliniteMeOH-Dox formulation holds promise for breast cancer treatment and warrants further investigation.
阿霉素是最常见的广谱化疗药物之一。然而，由于脱靶积累和选择性问题，其疗效有限。在本研究中，我们比较了阿霉素重新包装制剂高岭土甲醇-阿霉素与阿霉素单一疗法的抗癌效果和生物相容性。使用透射电子显微镜、动态光散射、zeta电位、傅里叶变换红外光谱、x射线衍射和体外药物释放对该制剂进行了广泛测试。MTT法测定了体外MCF-7细胞生长抑制情况。体内试验涉及20只未处理的小鼠和40只接种艾氏实体瘤的小鼠。对肿瘤大小进行了18天的监测。在所有实验组中，通过评估氧化应激、组织病理学和彗星试验，对肿瘤和心脏组织的细胞毒性和遗传毒性进行了评估。我们发现高岭土甲醇-阿霉素在尺寸、电荷、形状、高负载效率（90.16%）和pH依赖性释放方面具有许多优势。MTT试验表明，该制剂在生长抑制和选择性方面优于阿霉素。在体内，研究表明高岭土甲醇-阿霉素使肿瘤缩小了86.075%，而游离阿霉素为60.379%。组织学分析表明，高岭土甲醇-阿霉素可减小小鼠肿瘤大小、转移以及致癌性氧化应激和炎症，且不会伤害未处理的小鼠。基于所获得的数据，高岭土甲醇-阿霉素制剂在乳腺癌治疗方面具有前景，值得进一步研究。
