Khodarahmi Ghazal, Sabeti Bahare, Chekin Fereshteh
Department of Pharmacy, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran.
Department of Chemistry, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran.
J Mater Sci Mater Med. 2025 May 31;36(1):46. doi: 10.1007/s10856-025-06901-7.
Lung cancer is the leading cause of cancer deaths worldwide. Everolimus (Eve) was observed to upregulate the expression of phosphatase and tensin homolog and microRNA-4328 and inhibits the proliferation and migration of A549 cells. In the present study, a new nanocarrier based on composite containing chitosan (CS), carbon nanotubes (CNT) and ordered mesoporous (OMC) was used to load the anticancer drug everolimus (EVE). The existence of EVE on CNT/OMC/CS nanocarrier is confirmed by FE-SEM images, Raman, UV-Vis, FT-IR, BET and TGA analyses. The results showed that the introduction of CS improved the drug loading by 89.4% at pH 7.0, time 2 h and EVE to CNT/OMC/CS ratio of 1.5. Moreover, release study of EVE showed that 15.2% of EVE is released from EVE@CNT/OMC/CS at pH=7.4 for 15 h, while 78.9% of EVE is released at pH = 4.5. After 25 h, 16.8% and 88.0% of EVE were released at pH 7.4 and 4.5, respectively. Based on the MTT assay results, CNT/OMC/CS exhibited negligible cytotoxicity and good compatibility on the A549 lung cancer cell line. The cytotoxicity of the EVE@CNT/OMC/CS (IC50 of ~9 μg/mL) on the A549 cell line was higher as compared to free Eve drug (IC50 of ~13 μg/mL) after 48 h exposure time. All the data confirmed the synergistic effect of EVE in combination with CNT/OMC/CS could serve as an ideal candidate in treating lung cancer.
肺癌是全球癌症死亡的主要原因。观察到依维莫司（Eve）可上调磷酸酶和张力蛋白同源物以及微小RNA-4328的表达，并抑制A549细胞的增殖和迁移。在本研究中，一种基于壳聚糖（CS）、碳纳米管（CNT）和有序介孔材料（OMC）复合材料的新型纳米载体被用于负载抗癌药物依维莫司（EVE）。通过场发射扫描电子显微镜（FE-SEM）图像、拉曼光谱、紫外可见光谱、傅里叶变换红外光谱（FT-IR）、比表面积分析仪（BET）和热重分析（TGA）等分析方法证实了EVE存在于CNT/OMC/CS纳米载体上。结果表明，在pH值为7.0、时间为2小时且EVE与CNT/OMC/CS的比例为1.5的条件下，CS的引入使载药量提高了89.4%。此外，EVE的释放研究表明，在pH = 7.4的条件下，15.2%的EVE在15小时内从EVE@CNT/OMC/CS中释放出来，而在pH = 4.5时，78.9%的EVE被释放出来。25小时后，在pH 7.4和4.5条件下，分别有16.8%和88.0%的EVE被释放出来。基于MTT法检测结果，CNT/OMC/CS对A549肺癌细胞系的细胞毒性可忽略不计且具有良好的相容性。在暴露48小时后，EVE@CNT/OMC/CS对A549细胞系的细胞毒性（IC50约为9μg/mL）高于游离依维莫司药物（IC50约为13μg/mL）。所有数据证实，EVE与CNT/OMC/CS联合使用的协同效应使其成为治疗肺癌的理想候选药物。
