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包裹多西他赛的铁磁性海藻酸盐-壳聚糖纳米颗粒对人外周血单个核细胞和MCF-7乳腺癌细胞的副作用及疗效评估

Evaluation of Side Effects and Efficacy of Ferromagnetic Alginate-Chitosan Nanoparticles Encapsulating Docetaxel on PBMCs and MCF-7 Breast Cancer Cells.

作者信息

Shekari Marand Robab, Jafarian Vahab, Bahari Abbas, Ghajari Yasaman, Fardood Saeid Taghavi

机构信息

Department of Biology, Faculty of Sciences, University of Zanjan, Zanjan, Iran.

Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Iran.

出版信息

J Biochem Mol Toxicol. 2025 Mar;39(3):e70178. doi: 10.1002/jbt.70178.

DOI:10.1002/jbt.70178
PMID:40040436
Abstract

Docetaxel is a vital anticancer drug that despite its effectiveness, is associated with side effects in patients. The creation of an innovative docetaxel delivery system has received a lot of attention as a means of addressing issues including uncontrolled drug release, and nonspecific drug distribution with high toxicity. Here, the probable side effects and efficacy of dual-targeted alginate/chitosan coated magnetic nanoparticles encapsulating docetaxel on peripheral blood mononuclear cells (PBMCs) and breast cancer cells (MCF-7) were evaluated. The formulated nanoparticles were 23-56 nm in size, had a spherical shape, and a smooth surface. Drug release investigation showed a slow release rate for encapsulated docetaxel during 4 days. Cytotoxicity on the MCF-7 cell line was increased compared to the free drug and IC reduced about 26-fold after 72 h. The monitoring of Bax and Bcl-2 showed that the expression pattern was altered to disturb the equilibrium of anti-versus apoptotic genes. IL-1β was downregulated in the encapsulated group. The amount of Apoptosis was not significantly different in PBMCs, but the necrosis rate increased after treatment with encapsulated drug. According to the results, the newly formulated drug offers an innovative approach to enhancing therapeutic efficacy and can be considered an appropriate alternative for docetaxel in cancer treatment.

摘要

多西他赛是一种重要的抗癌药物,尽管其疗效显著,但会给患者带来副作用。作为解决包括药物释放不受控制、非特异性药物分布以及高毒性等问题的一种手段,创新的多西他赛递送系统的研发受到了广泛关注。在此,评估了包裹多西他赛的双靶向海藻酸盐/壳聚糖包被磁性纳米颗粒对外周血单个核细胞(PBMC)和乳腺癌细胞(MCF-7)可能产生的副作用及疗效。所制备的纳米颗粒尺寸为23 - 56纳米,呈球形,表面光滑。药物释放研究表明,包裹的多西他赛在4天内呈现缓慢释放速率。与游离药物相比,对MCF-7细胞系的细胞毒性增加,72小时后半数抑制浓度(IC)降低了约26倍。对Bax和Bcl-2的监测表明,其表达模式发生改变,从而扰乱了抗凋亡基因与促凋亡基因之间的平衡。在包裹组中,白细胞介素-1β(IL-1β)表达下调。PBMC中的凋亡量无显著差异,但用包裹药物处理后坏死率增加。根据研究结果,新制备的药物为提高治疗效果提供了一种创新方法,可被视为癌症治疗中多西他赛的合适替代物。

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