Department of Cell Biology, Institute of Biological Sciences, University of Brasília, Brasília 70910-900, DF, Brazil.
Postgraduate Program of Molecular Pathology, School of Medicine, University of Brasília, Brasília 70910-900, DF, Brazil.
Molecules. 2022 Aug 2;27(15):4920. doi: 10.3390/molecules27154920.
Cancer is one of the most lethal diseases in the world, and the development and improvement of treatments used in cancer therapies are extremely important for a better quality of life for patients. In view of the current problems in drug administration such as low solubility and adverse effects, the activity of a solid lipid nanoparticle containing docetaxel (SLN-DTX), a drug already used in conventional therapies, was evaluated in a cell line (MDA-MB-231) of one of the most aggressive types of breast cancer with the worst prognosis, triple-negative breast cancer. Viability tests indicated that SLN-DTX has a greater dependence on the treatment dose when compared to the free drug, which indicates a more controlled release of the drug, and both reduced viability by around 50% at a concentration of 1 µg/mL after 72 h. Transmission electron microscopy (TEM) and confocal and light microscopy analyses indicated that after treatment the cells enter a mitotic catastrophe, characteristic of antimitotic drugs that usually make cells progress to death or senescence. Cells treated with both DTX and SLN-DTX showed significant inhibition of mobility, 73.6% and 66.5% when treated with SLN-DTX and DTX, respectively, compared to the 11.4% of the control after 72 h, characteristics that are very relevant in tumor development and progression. SLN-DTX demonstrated its great potential as a nanocarrier by maintaining and improving the drug's action in the MDA-MB-231 cell line.
癌症是世界上最致命的疾病之一,开发和改进癌症治疗中使用的治疗方法对于提高患者的生活质量至关重要。鉴于目前药物给药存在的问题,如溶解度低和副作用大,评估了一种含有多西紫杉醇(SLN-DTX)的固体脂质纳米粒(SLN-DTX)的活性,多西紫杉醇是一种已在常规疗法中使用的药物,在一种侵袭性最强、预后最差的三阴性乳腺癌(MDA-MB-231)细胞系中进行了评估。细胞活力试验表明,与游离药物相比,SLN-DTX 对治疗剂量的依赖性更大,这表明药物的释放更受控,在 1μg/ml 浓度下 72 小时后,两者的细胞活力都降低了约 50%。透射电子显微镜(TEM)和共聚焦及明场显微镜分析表明,治疗后细胞进入有丝分裂灾难,这是抗有丝分裂药物的特征,通常使细胞死亡或衰老。用 DTX 和 SLN-DTX 处理的细胞表现出明显的迁移抑制,用 SLN-DTX 和 DTX 处理的细胞分别为 73.6%和 66.5%,而对照组 72 小时后为 11.4%,这些特性在肿瘤的发展和进展中非常重要。SLN-DTX 作为纳米载体,通过维持和提高药物在 MDA-MB-231 细胞系中的作用,显示出了巨大的潜力。