Department of Chemistry, College of Science, Jouf University, Sakaka, Aljouf, 72341, Saudi Arabia.
Protein Research Department, Genetic Engineering and Biotechnology Research Institute GEBRI, City of Scientific Research and Technological Applications (SRTA city), New Borg El-Arab, Alexandria, 21934, Egypt.
Sci Rep. 2024 Oct 22;14(1):24804. doi: 10.1038/s41598-024-74604-0.
It is imperative to explore new biocompatible drugs with low toxicity for use in medicinal fields such as fighting tumors. Bovine lactoperoxidase (BLPO) stems from the most important enzymes in the bovine whey that provide a proper pattern for nano-formulation with nanomaterials. LPO is a suitable protein to be coated or adsorbed to alginate modified graphene oxide (GO-SA), which forms the modified GO-SA-LPO hybrid structure. This novel combination provides LPO stability with strong anticancer effects and boosts immunity response. The characterization results obtained from different techniques confirmed a successful LPO adsorption on the GO-SA composite surface. Moreover, nano-formulation of LPO with GO-SA composite exhibited a reduction in its size and overall charge. In addition, the experimental results showed greater LPO activity stability in the modified GO-SA-LPO nanocombination than free LPO after storage for 10 weeks at 4 °C. The in vitro study, a crucial step in the validation of our approach, demonstrated that the modified GO-SA-LPO nanocombination showed a potent anticancer selectivity toward colon cancer cell lines more than GO-SA composite or free form of LPO, which enhanced in a dose-dependent manner with high safety manner against normal cells. The apoptotic effect of this novel nanocombination was confirmed by the greatest variations in the expression of both well-known apoptosis genes (p53 and Bcl-2), severe changes in the cellular morphology, DNA fragmentation, and nuclear staining with fluorescence yellow and orange of the target cancer cells. Also, this superior efficacy of the modified GO-SA-LPO nanocombination was induced by suppressing some pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin (IL-6), and necrosis factor-kappa B (NF-ĸB). Our observations presented that the modified nanocombination of LPO may offer a novel remedy for treating colon tumors via induced apoptosis pathway, inflammation reduction, and immune response improvement.
探索具有低毒性的新型生物相容性药物用于医学领域，如抗肿瘤，这是当务之急。牛乳过氧化物酶（BLPO）源自牛乳中的最重要的酶，为纳米制剂提供了与纳米材料形成合适模式的纳米制剂。LPO 是一种合适的蛋白质，可以被包裹或吸附到经藻酸钠修饰的氧化石墨烯（GO-SA）上，形成修饰的 GO-SA-LPO 杂化结构。这种新型组合提供了 LPO 的稳定性和强大的抗癌作用，并增强了免疫反应。不同技术获得的表征结果证实了 LPO 成功吸附在 GO-SA 复合表面上。此外，LPO 与 GO-SA 复合的纳米制剂显示出其尺寸和总电荷的减小。此外，实验结果表明，在 4°C 下储存 10 周后，修饰的 GO-SA-LPO 纳米组合中的 LPO 活性稳定性比游离 LPO 更高。体外研究是验证我们方法的关键步骤，表明修饰的 GO-SA-LPO 纳米组合对结肠癌细胞系的抗癌选择性比 GO-SA 复合材料或游离形式的 LPO 更强，并且以剂量依赖性方式增强，对正常细胞具有高安全性。这种新型纳米组合的凋亡作用通过两个众所周知的凋亡基因（p53 和 Bcl-2）的表达变化最大、细胞形态严重变化、DNA 片段化以及目标癌细胞的核染色（用黄色和橙色荧光）得到证实。此外，修饰的 GO-SA-LPO 纳米组合的这种优越功效是通过抑制一些促炎细胞因子，包括肿瘤坏死因子-α（TNF-α）、白细胞介素（IL-6）和核因子-κB（NF-κB）来诱导的。我们的观察结果表明，LPO 的修饰纳米组合可能通过诱导细胞凋亡途径、减轻炎症和改善免疫反应，为治疗结肠癌提供一种新的治疗方法。
