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介孔磁性纳米粒子负载伊达比星的制备及其对癌细胞系凋亡和细胞毒性的影响研究。

Development of mesoporous magnetic nanoparticles supported idarubicin and investigation of apoptotic and cytotoxic effects on cancer cell lines.

机构信息

Department of Medical Biochemistry, Gaziantep University, Gaziantep, 27310, Türkiye.

Department of Chemistry and Chemical Process Technologies, Mersin Tarsus Organized Industrial Zone Technical Sciences Vocational School, Tarsus University, Mersin, 33100, Türkiye.

出版信息

Mol Biol Rep. 2024 Sep 11;51(1):975. doi: 10.1007/s11033-024-09914-7.

Abstract

BACKGROUND

Many methods are used for cancer treatment, especially chemotherapy. In addition to the their therapeutic effects, chemotherapeutic drugs also have serious disadvantages, such as not being cell and tissue-specific, causing toxicity in many tissues, and developing drug resistance. Many methods, especially nanocarriers, have been designed to overcome these disadvantages.

METHODS AND RESULTS

In this study, we synthesized mesoporous silica iron oxide nanoparticles with different pore diameters and loaded idarubicin (6MFeO-NH-IDA and 35MFeO-NH-IDA). The synthesized molecules were characterized using FT-IR, XRD, and SEM methods. The cytotoxic effects of unbound idarubicin and idarubicin-loaded nanoparticles on MCF7 and HL-60 cell lines were examined by MTT test. Additionally, the expression of anti-apoptotic (Survivin and BCL-2) and apoptotic (BAX, PUMA, and NOXA) genes of the nanoparticles were measured by PCR method. As a result of the analyses, it was seen that nanoparticles with the desired properties and sizes were synthesized. In MTT analysis, it was observed that both nanoparticles dramatically decreased the IC value in cell lines. However, the 35MFeO-NH-IDA molecule was found to have lower IC values. IC values ​​for pristine IDA, 6MFeO-NH, and 35MFeO-NH at 24 h were found to be 3.56, 1.24 and 0.25 µM in the MCF7 cell line and 4.15, 1.16 and 0.34 µM in the HL-60 cell line, respectively. Additionally, apoptotic gene expression increased, and anti-apoptotic gene expression decreased.

CONCLUSIONS

Our study demonstrates that the effectiveness of idarubicin can be significantly enhanced by its application with mesoporous nanocarriers. This enhancement is attributed to the controlled release of idarubicin from the nanocarrier, which circumvents drug resistance mechanisms, improves drug solubility, and increases the drug-carrying capacity per unit volume due to the porous structure of the carrier. These findings underscore the potential of the synthesized nanocarrier in cancer treatment and provide a clear direction for future research in this field.

摘要

背景

癌症的治疗方法有很多,特别是化疗。除了治疗效果外,化疗药物还存在严重的缺点,如非细胞和组织特异性,导致许多组织毒性,并产生耐药性。许多方法,特别是纳米载体,已被设计用于克服这些缺点。

方法和结果

在这项研究中,我们合成了具有不同孔径的介孔硅氧化铁纳米粒子,并负载伊达比星(6MFeO-NH-IDA 和 35MFeO-NH-IDA)。通过傅里叶变换红外光谱(FT-IR)、X 射线衍射(XRD)和扫描电子显微镜(SEM)对合成分子进行了表征。通过 MTT 试验检测游离伊达比星和载药纳米粒子对 MCF7 和 HL-60 细胞系的细胞毒性作用。此外,通过 PCR 法测量纳米粒子的抗凋亡(Survivin 和 BCL-2)和凋亡(BAX、PUMA 和 NOXA)基因的表达。结果表明,合成了具有所需性质和尺寸的纳米粒子。在 MTT 分析中,观察到两种纳米粒子都显著降低了细胞系中的 IC 值。然而,35MFeO-NH-IDA 分子的 IC 值较低。在 MCF7 细胞系中,未修饰的 IDA、6MFeO-NH 和 35MFeO-NH 在 24 小时的 IC 值分别为 3.56、1.24 和 0.25 µM,在 HL-60 细胞系中分别为 4.15、1.16 和 0.34 µM。此外,凋亡基因表达增加,抗凋亡基因表达减少。

结论

本研究表明,介孔纳米载体可显著增强伊达比星的疗效。这种增强归因于伊达比星从纳米载体中的控释,该控释绕过了耐药机制,提高了药物溶解度,并由于载体的多孔结构增加了单位体积的载药量。这些发现强调了合成纳米载体在癌症治疗中的潜力,并为该领域的未来研究提供了明确的方向。

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