将N-羟基琥珀酰亚胺功能化的铁氧化物纳米颗粒与5-氟尿嘧啶结合,用于通过DNA修复紊乱进行恶性肝癌细胞的高温治疗。
N-Hydroxysuccinamide functionalized iron oxide nanoparticles conjugated with 5-flurouracil for hyperthermic therapy of malignant liver cancer cells by DNA repair disruption.
发表日期:2023 Jul 31
作者:
Subha Veeramani, Lavanya Chandrababu, Ilangovan Rajangam, N Rajmuhon Singh, Latifah Al-Humaid, Nora Dahmash Al-Dahmash, Ramachandran Balaji, Narendhar Chandrasekar, Michael Taeyoung Hwang
来源:
Int J Biol Macromol
摘要:
由于其生物相容性、超顺磁行为、表面可调性和化学稳定性,磁化氧化亚铁纳米颗粒是生物和生物医学应用的理想材料。本研究文章阐述了制备、功能化、表征和应用Fe3O4纳米颗粒的方法概述。超顺磁纳米颗粒被研究其热疗性质。所提出的热疗机制是通过损伤负责DNA修复的蛋白质,从而直接通过增加癌细胞周围的温度加速癌细胞的DNA损伤。在本研究中,使用N-羟基琥珀酰亚胺有机分子功能化的超顺磁氧化亚铁(Fe3O4)纳米颗粒(SPIONs)和抗癌药物5-氟尿嘧啶。使用紫外分析可以实现351 nm的特定吸收率。磁性Fe3O4纳米颗粒具有立方结晶结构。FE-SEM(场发射扫描电子显微镜)与EDAX(能量色散X射线分析)分析显示,SPION的尺寸约为30-100 nm范围,化学组成的百分比按Fe、O、C的顺序较高。粒径分析显示,SPION带正电荷,为+9.9 mV,其电导率为0.826 mS/cm。体外对Hep-G2细胞(肝癌细胞)的抗癌活性分析表明,功能化的5-氟尿嘧啶Fe3O4纳米颗粒的抑制率高于裸Fe3O4纳米颗粒。将Fe3O4纳米颗粒研究其在两种不同频率下的热疗能力,分别为3.05×106 kAm-1s-1和4.58×106 kAm-1s-1。在低磁场下,裸Fe3O4需要10 mg来提高温度超过42°- 45 °C,在高磁场下,仅需用6 mg即可达到相同温度。功能化的5-氟尿嘧啶Fe3O4显示在低磁场下需要6 mg来提高热疗温度,在高磁场下需要3 mg来提高温度超过42°- 45 °C。加入不同浓度和磁性成分,则可以调控加热速率和随时间达到的温度。超过此浓度,观察到细胞死亡率增加。磁化分析显示饱和和低剩余磁化,使其非常适合临床应用。版权所有©2023 Elsevier B.V.发布。
Magnetized iron oxide nanoparticles are ideal materials for biological and biomedical applications due to their biocompatibility, super paramagnetic behavior, surface capability, and chemical stability. This research article is narrating the overview of methodologies of preparation, functionalization, characterization and applications of Fe3O4 nanoparticles. Super paramagnetic nanoparticles are studied for their hyperthermia properties. The proposed mechanism behind the hyperthermia was damaging the proteins responsible for DNA repair thereby, directly accelerating the DNA damages on cancer cells by increasing the temperature in the vicinity of the cancer cells. In this study, super paramagnetic iron oxide (Fe3O4) nanoparticles (SPIONs) and anti-cancer drug, 5-fluorouracil, functionalized with N-Hydroxysuccinimide organic molecules. A specific absorption rate at 351 nm can be achieved using UV analysis. The magnetic Fe3O4 nanoparticles had a cubic crystalline structure. FE-SEM(field emission scanning Electron microscopy) with EDAX(energy dispersive X-ray analysis) analysis shows that the size of the SPION was about 30-100 nm range and the percentage of chemical compositions was higher in the order of Fe, O, C. for particle size analysis, the SPION were positively charged derived at +9.9 mV and its conductivity is measured at 0.826 mS/cm. In-vitro anti-cancerous activity analysis in Hep-G2 cells (liver cancer cells) shows that the 5-fluorouracil functionalized SPIONs have higher inhibition rate than the bare Fe3O4 nanoparticles. The Fe3O4 nanoparticles were studied for their hyperthermic abilities at two different frequencies such as 3.05 × 106 kAm-1s-1 and 4.58 × 106 kAm-1s-1.The bare Fe3O4 at low magnetic field, 10 mg was required to raise the temperature above 42°- 45 °C and at high magnetic field, 6 mg was enough to raise the same temperature. The 5-fluorouracil functionalized Fe3O4 shows that at low magnetic field, 6 mg is required to raise the hyperthermia temperature and at high magnetic field, 3 mg is required to raise the temperature above 42°- 45 °C. the rate of heating and the temperature achieved with time can be tuned with concentrations as well as magnetic component present in the Fe3O4 nanoparticles. Beyond this concentration, the rate of cell death was observed to increase. The saturation and low residual magnetization were revealed by the magnetization analysis, making them well suited for clinical applications.Copyright © 2023. Published by Elsevier B.V.