Sedky Nada K, Arafa Kholoud K, Abdelhady Manal M M, Issa Marwa Y, Abdel-Kader Nour M, Mahdy Noha Khalil, Mokhtar Fatma A, Alfaifi Mohammad Y, Fahmy Sherif Ashraf
Department of Biochemistry, School of Life and Medical Sciences, University of Hertfordshire Hosted by Global Academic Foundation, R5 New Garden City, New Administrative Capital, Cairo 11835, Egypt.
Drug Design and Discovery Lab, Zewail City for Science, Technology and Innovation, Cairo 12578, Egypt.
Pharmaceutics. 2023 Sep 22;15(10):2367. doi: 10.3390/pharmaceutics15102367.
Currently, the main pillars in treating breast cancer involve tumorectomy pursued by hormonal, radio, or chemotherapies. Nonetheless, these approaches exhibit severe adverse effects and might suffer from tumor recurrence. Therefore, there is a considerable demand to fabricate an innovative controlled-release nano-delivery system to be implanted after tumor surgical removal to guard against cancer recurrence. In addition, combining platinum-based drugs with phytochemicals is a promising approach to improving the anticancer activity of the chemotherapeutics against tumor cells while minimizing their systemic effects. This study designed polycaprolactone (PCL)-based electrospun nanofiber mats encapsulating nedaplatin (N) and alkaloid-rich fraction (L). In addition to physicochemical characterization, including average diameters, morphological features, degradation study, thermal stability, and release kinetics study, the formulated nanofibers were assessed in terms of cytotoxicity, where they demonstrated potentiated effects and higher selectivity towards breast cancer cells. The dual-loaded nanofiber mats (N + L@PCL) demonstrated the highest antiproliferative effects against MCF-7 cells with a recorded IC50 of 3.21 µg/mL, as well as the topmost achieved selectivity index (20.45) towards cancer cells amongst all the tested agents (N, L, N@PCL, and L@PCL). This indicates that the dual-loaded nanofiber excelled at conserving the normal breast epithelial cells (MCF-10A). The combined therapy, N + L@PCL treatment, resulted in a significantly higher percent cell population in the late apoptosis and necrosis quartiles as compared to all other treatment groups (-value of ≤0.001). Moreover, this study of cell cycle kinetics revealed potentiated effects of the dual-loaded nanofiber (N + L@PCL) at trapping more than 90% of cells in the sub-G1 phase and reducing the number of cells undergoing DNA synthesis in the S-phase by 15-fold as compared to nontreated cells; hence, causing cessation of the cell cycle and confirming the apoptosis assay results. As such, our findings suggest the potential use of the designed nanofiber mats as perfect implants to prevent tumor recurrence after tumorectomy.
目前，治疗乳腺癌的主要方法包括肿瘤切除术后进行激素、放射或化学疗法。然而，这些方法会产生严重的副作用，并且可能会出现肿瘤复发。因此，迫切需要制造一种创新的控释纳米递送系统，在肿瘤手术切除后植入，以防止癌症复发。此外，将铂类药物与植物化学物质相结合是一种很有前景的方法，可以提高化疗药物对肿瘤细胞的抗癌活性，同时将其全身副作用降至最低。本研究设计了基于聚己内酯（PCL）的电纺纳米纤维垫，其中包裹了奈达铂（N）和富含生物碱的组分（L）。除了进行包括平均直径、形态特征、降解研究、热稳定性和释放动力学研究在内的物理化学表征外，还对制备的纳米纤维进行了细胞毒性评估，结果显示它们对乳腺癌细胞具有增强的作用和更高的选择性。双负载纳米纤维垫（N + L@PCL）对MCF-7细胞表现出最高的抗增殖作用，记录的IC50为3.21 µg/mL，并且在所有测试药物（N、L、N@PCL和L@PCL）中对癌细胞的选择性指数最高（20.45）。这表明双负载纳米纤维在保护正常乳腺上皮细胞（MCF-10A）方面表现出色。联合疗法N + L@PCL治疗导致晚期凋亡和坏死四分位数中的细胞群体百分比显著高于所有其他治疗组（-值≤0.001）。此外，这项细胞周期动力学研究表明，双负载纳米纤维（N + L@PCL）具有增强的作用，与未处理的细胞相比，它能将超过90%的细胞捕获在亚G1期，并使S期进行DNA合成的细胞数量减少15倍；因此，导致细胞周期停止并证实了凋亡检测结果。因此，我们的研究结果表明，所设计的纳米纤维垫有可能作为完美的植入物用于防止肿瘤切除术后的肿瘤复发。
