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冷大气等离子体与负载亚甲蓝的纳米胶束对人胶质母细胞瘤细胞治疗的协同作用:一项体外及分子动力学研究

Synergistic effect of cold atmospheric plasma and methylene blue loaded nano micelles on treating human glioblastoma cells: An in vitro and molecular dynamics study.

作者信息

Ahmadi Elahe, Imanparast Armin, Hoseini Mehdi, Naseri Shahrokh, Soudmand Salarabadi Samaneh, Sazgarnia Ameneh

机构信息

Medical Physics Research Center, Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Department of Medical Physics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Iran J Basic Med Sci. 2025;28(3):299-309. doi: 10.22038/ijbms.2024.79858.17304.

Abstract

OBJECTIVES

One of the most recent cancer treatment methods is cold atmospheric plasma (CAP), which destroys cancer cells without affecting healthy cells. Also, the created photons in the CAP flame can be used to excite a proper photosensitizing agent (PS). Therefore, using nano micelle systems containing a proper photosensitizer may be beneficial in raising the treatment efficacy of CAP. In this study, we utilized molecular dynamics (MD) simulation to optimize a nano micellar system containing methylene blue to take advantage of the induced photodynamic effect of a CAP generator with helium gas on a glioblastoma cell line.

MATERIALS AND METHODS

Some micelle properties were first determined and optimized by MD with GROMACS software. Then, micelles containing methylene blue (Micelle-MB) and free methylene blue (MB) at various concentrations were prepared. Singlet oxygen dosimetry using 1,3-diphenylisobenzofuran (DPBF)was performed in the presence and absence of Micelle-MB and MB. Subsequently, the cytotoxicity of MB and Micelle-MB was evaluated on U87-MG cancer cells, and their half-maximal inhibitory concentrations (IC) were determined. After 48 hr of treatment, the percentage of cell survival was determined using the MTT test. The experiments were repeated at least three times. The synergy index was selected to compare the results.

RESULTS

Treatment with CAP and MB reduced the survival rate compared to the PS-free group with CAP. Results of singlet oxygen dosimetry showed that Micelle-MB might be more efficient in producing ROS. CAP treatment with Micelle-MB resulted in more cell death than free MB. In addition, cell viability decreased in Micelle-MB groups with increasing irradiation time in the three investigated irradiation times.

CONCLUSION

Using Micelle-MB in the CAP treatment improves treatment efficiency in the U87-MG cell line.

摘要

目的

冷大气等离子体(CAP)是最新的癌症治疗方法之一,它能在不影响健康细胞的情况下破坏癌细胞。此外,CAP火焰中产生的光子可用于激发合适的光敏剂(PS)。因此,使用含有合适光敏剂的纳米胶束系统可能有助于提高CAP的治疗效果。在本研究中,我们利用分子动力学(MD)模拟优化了一种含有亚甲蓝的纳米胶束系统,以利用氦气CAP发生器对胶质母细胞瘤细胞系的诱导光动力效应。

材料与方法

首先使用GROMACS软件通过MD确定并优化了一些胶束特性。然后,制备了不同浓度的含亚甲蓝胶束(Micelle-MB)和游离亚甲蓝(MB)。在有和没有Micelle-MB及MB的情况下,使用1,3-二苯基异苯并呋喃(DPBF)进行单线态氧剂量测定。随后,评估了MB和Micelle-MB对U87-MG癌细胞的细胞毒性,并确定了它们的半数最大抑制浓度(IC)。处理48小时后,使用MTT试验测定细胞存活率。实验至少重复三次。选择协同指数来比较结果。

结果

与无PS的CAP组相比,CAP和MB处理降低了存活率。单线态氧剂量测定结果表明,Micelle-MB在产生活性氧方面可能更有效。用Micelle-MB进行CAP处理比游离MB导致更多细胞死亡。此外,在三个研究的照射时间中,Micelle-MB组的细胞活力随着照射时间的增加而降低。

结论

在CAP治疗中使用Micelle-MB可提高U87-MG细胞系的治疗效率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5fa/11790199/854df1c6fe29/IJBMS-28-299-g001.jpg

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