Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Department of Biochemistry, Shahrood Branch, Islamic Azad University, Shahrood, Iran.
Naunyn Schmiedebergs Arch Pharmacol. 2024 Sep;397(9):6623-6631. doi: 10.1007/s00210-024-03042-6. Epub 2024 Mar 14.
Applying nanotechnology to design drug delivery systems is a promising turning point in cancer treatment strategies. In the current study, Lawson, a nonpolar anticancer phytochemical, was entrapped into β-cyclodextrin polymer to evaluate its selective cytotoxicity in several types of human cancer cell lines including MCF-7, AGS, A549, and PC3. The Lawson-loaded β-cyclodextrin nanocarriers (LB-NCs) were produced by applying a high-energy ultrasound-mediated homogenization technique. The LB-NCs were characterized by applying dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), zeta potential, and field emission scanning electron microscopy (FESEM) analysis. Also, the selective cytotoxic impact of the LB-NCs was studied by conducting the MTT assay on human MCF-7, AGS, A549, and PC3 cancer cell lines. Finally, the type of cellular death was evaluated by measuring the cell cycle status and apoptotic gene expression profile of the treated MCF-7 cells by conducting flow cytometry and Q-PCR methods, respectively. The synthesized negatively charged (- 23.8 mV) nanoparticles (348.12 nm) exhibited apoptotic activity in the human breast MCF-7 cancer cells by upregulating the apoptotic gene expression profile (Caspase 3, 8, and 9). The LB-NCs exhibited a significant selective cytotoxic effect on the human cancer cell lines compared with the normal HUVEC cells. However, variable toxic intensities were detected depending on the cancer cell type. Selective cancer cell-depended anticancer activity of the produced LB-NCs has the potential to be considered their safe efficient targeted anticancer activity. However, studying the animal cancer models has to be conducted to verify their selective toxicity and clarify the cellular death mechanism.
将纳米技术应用于设计药物传递系统是癌症治疗策略的一个有前途的转折点。在目前的研究中,劳森(Lawson),一种非极性抗癌植物化学物质,被包埋在β-环糊精聚合物中,以评估其在几种人类癌细胞系(包括 MCF-7、AGS、A549 和 PC3)中的选择性细胞毒性。通过应用高能超声介导的匀化技术制备劳森负载的β-环糊精纳米载体(LB-NCs)。通过动态光散射(DLS)、傅里叶变换红外光谱(FTIR)、zeta 电位和场发射扫描电子显微镜(FESEM)分析对 LB-NCs 进行了表征。还通过在人 MCF-7、AGS、A549 和 PC3 癌细胞系上进行 MTT 测定研究了 LB-NCs 的选择性细胞毒性作用。最后,通过流式细胞术和 Q-PCR 方法分别测量经处理的 MCF-7 细胞的细胞周期状态和凋亡基因表达谱,评估了细胞死亡的类型。合成的带负电荷(-23.8 mV)的纳米颗粒(348.12 nm)通过上调凋亡基因表达谱(Caspase 3、8 和 9)在人乳腺癌 MCF-7 癌细胞中表现出凋亡活性。LB-NCs 对人癌细胞系表现出显著的选择性细胞毒性作用,与正常 HUVEC 细胞相比。然而,根据癌细胞类型检测到不同的毒性强度。所产生的 LB-NCs 的选择性癌症依赖性抗癌活性有可能被认为是其安全有效的靶向抗癌活性。然而,必须进行动物癌症模型的研究,以验证其选择性毒性并阐明细胞死亡机制。