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碳纳米管/有序介孔碳/壳聚糖纳米复合材料作为一种有前景的载体,用于将依维莫司靶向递送至肺癌细胞。

Carbon nanotubes/ordered mesoporous carbon/chitosan nanocomposite as a promising carrier for everolimus targeted delivery toward lung cancer cells.

作者信息

Khodarahmi Ghazal, Sabeti Bahare, Chekin Fereshteh

机构信息

Department of Pharmacy, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran.

Department of Chemistry, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran.

出版信息

J Mater Sci Mater Med. 2025 May 31;36(1):46. doi: 10.1007/s10856-025-06901-7.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5720/12126314/8bc0acc12073/10856_2025_6901_Fig1_HTML.jpg

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