戊二醛包被磁性纳米颗粒对伊达柔比星的吸附及对HL-60细胞株的影响

H. Ulusal, F. Ulusal, Mehmet Akif Bozdayi, Bilgehan Güzel, S. Taysı, M. Tarakçıoğlu
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摘要

伊达柔比星是一种化疗药物,常用于治疗乳腺癌和急性白血病。本研究旨在将依阿霉素固定在戊二醛包被磁性纳米颗粒(MNP-GA)上,制备一种高稳定性、低毒性的药物。由于MNPS易于合成、成本低且无毒,我们预先释放了MNPS。在研究中,制备了磁铁矿(Fe3O4)纳米颗粒,并包覆戊二醛,采用傅里叶变换红外光谱(FT-IR)、x射线衍射图(XRD)和常规透射电镜(C-TEM)方法对其进行表征,并结合伊达柔比星(IDA)。采用MTT和ATP试验检测结合依达柔比星MNP-GA和游离依达柔比星对HL-60细胞株的细胞毒作用,并计算IC50值。流式细胞术检测细胞凋亡状态,聚合酶链反应(PCR)检测MDR1、Puma、NOXA、BAX、Survivin、BCL-2基因表达。结果发现,使用MNP后,IC50降低了5 ~ 7倍。PCR检测显示,MNP使凋亡基因表达增加,而MDR1和抗凋亡基因表达减少。流式细胞术检测发现细胞凋亡增加。MNP系统的使用减少了耐药性,因为它提供了药物的可控释放,并且由于其结构而阻止其从细胞中退出。
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Attachment of Idarubicin to Glutaraldehyde-coated Magnetic Nanoparticle and Investigation of its Effect in HL-60 Cell Line
Idarubicin is a chemotherapeutic drug frequently used to treat breast cancer and acute leukemia. This study aimed to immobilize idarubicin on glutaraldehyde (GA)-coated magnetic nanoparticles (MNP-GA) to prepare a drug with high stability and low toxicity. We prefreed MNPS because of their easy synthesis, low cost, and non-toxicity. In the study, magnetite (Fe3O4) nanoparticles were prepared, coated with glutaraldehyde, characterization processes were performed with Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction pattern (XRD), and Conventional transmission electron microscopy (C-TEM) methods, and idarubicin (IDA) was bound. The cytotoxic effects of idarubicin-bound MNP-GA and free idarubicin on HL-60 cell lines were determined by MTT and ATP tests, and IC50 values were calculated. Flow cytometry was used to evaluate apoptosis status, and the expression of MDR1, Puma, NOXA, BAX, Survivin, and BCL-2 genes were measured by the polymerase chain reaction (PCR). It was found that the IC50 decreased between 5 and 7 times with the use of MNP. In PCR tests, the expressions of apoptotic genes increased, while the expressions of MDR1 and anti-apoptotic genes were decreased in the use of MNP. Apoptosis was found to be increased in flow cytometry measurements. The use of MNP systems has reduced drug resistance since it provides controlled release of the drug and prevents its exit from the cell due to its structure.
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