一个对人肺癌细胞具有显著细胞毒性的小凹槽结合剂:柚皮素功能化银纳米颗粒的潜力。
A Minor Groove Binder with Significant Cytotoxicity on Human Lung Cancer Cells: The Potential of Hesperetin Functionalised Silver Nanoparticles.
发表日期:2023 Sep 18
作者:
Aparna Raj, Riju K Thomas, L Vidya, S Neelima, V M Aparna, C Sudarsanakumar
来源:
PHARMACOLOGY & THERAPEUTICS
摘要:
由于其治疗效果,天然药物修饰银(Ag)纳米颗粒(NPs)在药理学相关应用中引起了极大的兴趣。我们使用异黄酮作为还原剂和包覆剂合成了银纳米颗粒。本研究旨在讨论异黄酮修饰银纳米颗粒(H-AgNPs)在纳米医学领域中的相关性。该文章首先研究了H-AgNPs的抗癌活性,然后通过光谱和热力学技术研究了其与牛胸腺DNA(ctDNA)的相互作用。绿色合成的H-AgNPs具有稳定的球形结构,平均直径为10 ± 3 nm。通过紫外可见吸收、荧光染料置换实验、等温热量计和粘度测量,确定了H-AgNPs与ctDNA的复合物形成。这些实验得到的结合常数始终为104 Mol-1。熔融温度分析和FTIR测量证实H-AgNPs对ctDNA的结构变化很小。所有热力学变量和吸热结合性质都来自等温量热法实验。所有这些实验结果表明了H-AgNPs-ctDNA复合物的形成,并且结果一致验证了H-AgNPs的小沟结合模式。从相互作用研究中发现的结合常数和检测限1.8 μM表明H-AgNPs具有高的DNA检测效率。通过体外MTT细胞存活率测定和乳酸脱氢酶(LDH)测定确定了H-AgNPs对A549和L929细胞株的细胞毒性。细胞存活率和LDH酶释放实验证明H-AgNPs具有较高的抗癌活性。此外,H-AgNPs对肺癌细胞的LD50值为118.49 µl/ml,与成纤维细胞值(269.35 µl/ml)相比较低。总之,体外细胞毒性实验结果表明合成的纳米颗粒可以应用于癌症治疗。此外,我们发现H-AgNPs是一种小沟结合剂,并具有高的DNA检测效率。©2023. 作者,独家授权给Springer Science+Business Media,LLC,属于Springer Nature的一部分。
Natural drug functionalised silver (Ag) nanoparticles (NPs) have gained significant interest in pharmacology related applications due to their therapeutic efficiency. We have synthesised silver nanoparticle using hesperetin as a reducing and capping agent. This work aims to discuss the relevance of the hesperetin functionalised silver nanoparticles (H-AgNPs) in the field of nano-medicine. The article primarily investigates the anticancer activity of H-AgNPs and then their interactions with calf thymus DNA (ctDNA) through spectroscopic and thermodynamic techniques. The green synthesised H-AgNPs are stable, spherical in shape and size of 10 ± 3 nm average diameter. The complex formation of H-AgNPs with ctDNA was established by UV-Visible absorption, fluorescent dye displacement assay, isothermal calorimetry and viscosity measurements. The binding constants obtained from these experiments were consistently in the order of 104 Mol-1. The melting temperature analysis and FTIR measurements confirmed that the structural alterations of ctDNA by the presence of H-AgNPs are minimal. All the thermodynamic variables and the endothermic binding nature were acquired from ITC experiments. All these experimental outcomes reveal the formation of H-AgNPs-ctDNA complex, and the results consistently verify the minor groove binding mode of H-AgNPs. The binding constant and limit of detection of 1.8 μM found from the interaction studies imply the DNA detection efficiency of H-AgNPs. The cytotoxicity of H-AgNPs against A549 and L929 cell lines were determined by in vitro MTT cell viability assay and lactate dehydrogenase (LDH) assay. The cell viability and LDH enzyme release are confirmed that the H-AgNPs has high anticancer activity. Moreover, the calculated LD50 value for H-AgNPs against lung cancer cells is 118.49 µl/ml, which is a low value comparing with the value for fibroblast cells (269.35 µl/ml). In short, the results of in vitro cytotoxicity assays revealed that the synthesised nanoparticles can be considered in applications related to cancer treatments. Also, we have found that, H-AgNPs is a minor groove binder, and having high DNA detection efficiency.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.