合成壳聚糖聚乙二醇抗体复合物,用于在肺癌细胞系中递送伊马替尼

IF 3.2 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Mehrdad Kamali, Hanieh Jafari, Fatemeh Taati, Javad Mohammadnejad, Amin Daemi
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引用次数: 0

摘要

肺癌被称为最常见的癌症。虽然 Ramucirumab 抗体是治疗肺癌的二线药物,但肺间质压力过高限制了该抗体的作用。因此,伊马替尼是一种降低肺间质压力的化疗药物。遗憾的是,迄今为止,还没有报道过将雷莫芦单抗和伊马替尼同时用于癌症治疗的纳米系统。为了弥补这一不足,本文旨在设计一种壳聚糖纳米载体,该载体可装载伊马替尼并与拉莫单抗连接,从而选择性地与 A549 结合。因此,本文旨在开发一种用于治疗非小细胞肺癌(NSCLC)的聚合物纳米系统。首先,合成壳聚糖聚乙二醇纳米粒子,载入伊马替尼,然后使用拉穆单抗进行靶向治疗。然后,利用傅立叶变换红外光谱、TEM、DLS、ZETA电位和TGA技术对CS-PEG-Ab-Im进行表征。CS-PEG-Ab-Im 的尺寸为 25-30 nm,表面电荷为 13.1 mV,形状接近球形和圆柱形。利用 A549 细胞系评估了 CS-PEG-Ab-Im 的治疗潜力。结果表明,使用 IC50 浓度(100 纳摩尔)的 CS-PEG-Ab-Im 处理 A549 细胞 48 小时后,细胞存活率为 48%。此外,与游离伊马替尼相比,细胞凋亡率和细胞周期停滞率分别提高了 3 倍和 6 倍。此外,在酸性培养基中,CS-PEG-Ab-Im 在 1 小时内的伊马替尼释放率为 17%,是天然培养基中伊马替尼释放率的 5 倍。流式细胞仪的结果表明,纳米系统的凋亡效果优于游离伊马替尼和CS-PEG-Ab。此外,细胞凋亡结果显示,CS-PEG-Ab-Im 能使细胞在 G1 期凋亡 8.17%。因此,可以认为CS-PEG-Ab-Im是治疗NSCLC的理想纳米系统。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Synthesis of chitosan polyethylene glycol antibody complex for delivery of Imatinib in lung cancer cell lines

Synthesis of chitosan polyethylene glycol antibody complex for delivery of Imatinib in lung cancer cell lines

Lung cancer is known as the most common cancer. Although the Ramucirumab antibody is a second-line treatment for lung cancer, the high interstitial fluid pressure limits the antibody's performance. In this way, Imatinib is a chemotherapeutic drug to reduce the interstitial fluid pressure. Up to now, unfortunately, both Ramucirumab and imatinib have not been reported in one nanosystem for cancer therapy. To fulfill this shortcoming, this paper aims to design a chitosan nanocarrier that loads imatinib and attaches to Ramucirumab for selective bonding to A549. Therefore, this paper aims to develop a polymeric nanosystem for non-small cell lung cancer (NSCLC) treatment. In first, the chitosan polyethylene glycol nanoparticle is synthesized, loaded with imatinib, and then targeted using Ramucirumab. Afterwards, the CS-PEG-Ab-Im by FTIR, TEM, DLS, zeta potential, and TGA techniques are characterized. The size of CS-PEG-Ab-Im was 25–30 nm, its surface charge was 13.1 mV, and the shape of CS-PEG-Ab-Im was nearly spherical and cylindrical. The therapeutic potential of CS-PEG-Ab-Im was assessed using the A549 cell line. According to the obtained results, the cell viability was 48% after 48 h of treatment of A549 cells using the IC50 concentration of CS-PEG-Ab-Im (100 nanomolar). Moreover, the apoptosis and cell cycle arrest percentages were increased by 3 and 6 times, respectively, as compared to free imatinib. Furthermore, the release rate of imatinib from CS-PEG-Ab-Im in an acidic medium was 17% during 1 h, indicating five times the imatinib release in the natural medium. Eventually, the result of flow cytometry indicates the more apoptotic effect of nanosystem to free imatinib and CS-PEG-Ab. Besides, cell arresting result exhibits the CS-PEG-Ab-Im and causes cell arrested at G1 by %8.17. Thus, it can be concluded that CS-PEG-Ab-Im can be an ideal nanosystem in NSCLC treatment.

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来源期刊
CiteScore
5.80
自引率
2.80%
发文量
277
审稿时长
6-12 weeks
期刊介绍: The Journal of Biochemical and Molecular Toxicology is an international journal that contains original research papers, rapid communications, mini-reviews, and book reviews, all focusing on the molecular mechanisms of action and detoxication of exogenous and endogenous chemicals and toxic agents. The scope includes effects on the organism at all stages of development, on organ systems, tissues, and cells as well as on enzymes, receptors, hormones, and genes. The biochemical and molecular aspects of uptake, transport, storage, excretion, lactivation and detoxication of drugs, agricultural, industrial and environmental chemicals, natural products and food additives are all subjects suitable for publication. Of particular interest are aspects of molecular biology related to biochemical toxicology. These include studies of the expression of genes related to detoxication and activation enzymes, toxicants with modes of action involving effects on nucleic acids, gene expression and protein synthesis, and the toxicity of products derived from biotechnology.
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