Zoology Department, Faculty of Women for Arts Science and Education, Ain Shams University, 11757 Cairo, Egypt.
Group of Bionanotechnology and Molecular Cell Biology, Institute of Nanoscience and Nanotechnology, Kafrelsheikh University, 33516 Kafrelsheikh, Egypt.
Int J Biol Macromol. 2024 Nov;280(Pt 2):135854. doi: 10.1016/j.ijbiomac.2024.135854. Epub 2024 Sep 20.
This study aimed to assess the targeted nano-therapy of encapsulated cisplatin (Cis) and anthocyanin (Ant)-loaded multiwalled carbon nanotubes (CNT) coated with chitosan conjugated folic acid on breast MCF7 and liver HepG2 cancer cells. Zeta potential, UV-spectroscopy, FTIR, TEM, and SEM were used to evaluate CNT, its modified form (CNT Mod), CNT-loaded Cis NPs, CNT-loaded Ant NPs, and CNT- Cis + Ant NPs. All treatments induced apoptosis-dependent cytotoxicity in both cell lines as revealed functionally by the MTT assay, morphologically (DNA degradation) by acridine orange/ethidium bromide (AO/EB) double staining, and molecularly (Bax upregulation and Bcl2 downregulation) by real-time PCR, with best effect for the combined treatment (CNT- Cis + Ant NPs). This combined treatment also significantly reduced inflammation (low TNFα), migration (low MMP9 and high TIMP1), and angiogenesis (low VEGF), while significantly increasing antioxidant status (high Nrf2 and OH-1) in MCF7 and HepG2 cells compared to other treatments. Interestingly, cells treated with CNT Mod exhibited higher cytotoxic, apoptotic, anti-migratory, and anti-angiogenic potentials relative to CNT-treated cells. In conclusion, targeted nano-therapy of encapsulated cisplatin and anthocyanin-loaded carbon nanotubes coated with chitosan conjugated folic acid can efficiently combat breast and liver cancers by sustained release, in addition to its apoptotic, antioxidant, anti-inflammatory, anti-metastatic, and anti-angiogenic effects.
本研究旨在评估载顺铂(Cis)和花青素(Ant)的多壁碳纳米管(MWCNT)经壳聚糖偶联叶酸修饰后的靶向纳米治疗对乳腺癌 MCF7 和肝癌 HepG2 癌细胞的作用。通过zeta 电位、紫外光谱、傅里叶变换红外光谱、TEM 和 SEM 对 MWCNT、修饰后的 MWCNT(MWCNT Mod)、载 Cis NPs 的 MWCNT、载 Ant NPs 的 MWCNT 和载 Cis+Ant NPs 的 MWCNT 进行评估。MTT 检测结果显示,所有处理均在两种细胞系中诱导了凋亡依赖性细胞毒性,吖啶橙/溴化乙锭(AO/EB)双重染色显示形态学上的细胞凋亡(DNA 降解),实时 PCR 显示分子水平的(Bax 上调和 Bcl2 下调),联合治疗(MWCNT-Cis+Ant NPs)效果最佳。与其他治疗方法相比,这种联合治疗还显著降低了 MCF7 和 HepG2 细胞中的炎症(TNFα 水平降低)、迁移(MMP9 水平降低和 TIMP1 水平升高)和血管生成(VEGF 水平降低),同时显著增加了抗氧化状态(Nrf2 和 OH-1 水平升高)。有趣的是,与 MWCNT 处理的细胞相比,经 MWCNT Mod 处理的细胞表现出更高的细胞毒性、凋亡、抗迁移和抗血管生成潜力。总之,载顺铂和花青素的碳纳米管经壳聚糖偶联叶酸修饰后的靶向纳米治疗可通过持续释放有效对抗乳腺癌和肝癌,此外还具有凋亡、抗氧化、抗炎、抗转移和抗血管生成作用。