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

IF 2.8 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of Biochemical and Molecular Toxicology Pub Date : 2025-03-05 DOI:10.1002/jbt.70178
Robab Shekari Marand, Vahab Jafarian, Abbas Bahari, Yasaman Ghajari, Saeid Taghavi Fardood
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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 IC50 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.

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多西紫杉醇包封藻酸盐-壳聚糖纳米颗粒对PBMCs和MCF-7乳腺癌细胞的毒副作用和疗效评价
多西紫杉醇是一种重要的抗癌药物,尽管它有效,但对患者有副作用。创新多西紫杉醇给药系统的创建作为解决药物释放失控和高毒性非特异性药物分布等问题的一种手段受到了广泛关注。本研究评估了双靶向海藻酸盐/壳聚糖包被磁性纳米颗粒包封多西紫杉醇对外周血单核细胞(PBMCs)和乳腺癌细胞(MCF-7)的可能副作用和疗效。制备的纳米颗粒尺寸为23 ~ 56 nm,呈球形,表面光滑。药物释放试验显示,多西紫杉醇包封后4天内缓释。72h后,MCF-7细胞株的细胞毒性较游离药物增加,IC50降低约26倍。对Bax和Bcl-2的监测表明,其表达模式发生改变,破坏了抗凋亡基因的平衡。包封组IL-1β表达下调。细胞凋亡的数量在PBMCs中没有显著差异,但包膜药物治疗后坏死率增加。结果表明,新配制的药物提供了一种创新的方法来提高治疗效果,可以考虑作为多西紫杉醇治疗癌症的合适替代品。
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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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