多西他赛负载的固体脂质纳米颗粒(SLN-DTX)对体外胃腺癌的细胞毒性增强作用

IF 2.8 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Laís Vaz-Costa, Marina Arantes Radicchi, Caterynne Melo Kauffmann, Guilherme Sirimarco de Souza Silveira Tonelli, Igor Oliveira Santos, Kelly Grace Magalhães, Sônia Nair Báo
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引用次数: 0

摘要

胃癌是世界范围内死亡的主要原因之一。尽管最近癌症治疗取得了进展,但胃癌患者的治愈率和生存率几乎没有变化。传统化疗药物如多西他赛的使用受到一些缺点的限制,如脱发和血液毒性。本研究主要研究负载多西紫杉醇的固体脂质纳米颗粒(SLN-DTX)对胃腺癌细胞的抗肿瘤作用。SLN-DTX显示出对癌细胞(AGS)的细胞毒性,在处理24 h后,其IC50值低于游离DTX浓度,证明了纳米颗粒的有效性。形态学分析显示结构改变,包括细胞变圆和细胞质突起减少。SLN-DTX和DTX诱导微管、结合蛋白和核心断裂损伤,损害细胞粘附和增殖。他们还显示了细胞器(线粒体和溶酶体)和细胞代谢分析的变化。SLN-BLANK在AGS肿瘤谱系中没有表现出明显的毒性,其表现与未治疗的对照组相似。多西紫杉醇与固体脂质纳米颗粒(SLN-DTX)的结合显示出对胃腺癌细胞诱导细胞毒作用的显著效率,因为这种配方显示出有效的抗肿瘤活性。纳米结构的多西紫杉醇治疗除了改变与肿瘤进展相关的分子释放外,还引起形态学和代谢变化。这些发现支持SLN-DTX作为一种有前景的药物传递系统的潜在应用,为胃癌治疗提供了一种创新和有效的方法,同时可能减少与传统疗法相关的副作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Enhanced Cytotoxic Effects of Docetaxel-Loaded Solid Lipid Nanoparticles (SLN-DTX) on Gastric Adenocarcinoma In Vitro

Enhanced Cytotoxic Effects of Docetaxel-Loaded Solid Lipid Nanoparticles (SLN-DTX) on Gastric Adenocarcinoma In Vitro

Gastric cancer is one of the leading causes of mortality worldwide. Despite recent advances in cancer therapy, there has been little change in cure and survival rates in patients suffering from gastric cancer. The use of conventional chemotherapeutic agents such as docetaxel is limited by some disadvantages such as alopecia and hematotoxicity. This study focused on the antitumor effects of solid lipid nanoparticles loaded with docetaxel (SLN-DTX) on gastric adenocarcinoma cells. SLN-DTX showed cytotoxicity against cancer cells (AGS), demonstrating an IC50 value lower than the concentration of free DTX after 24 h of treatment, evidencing the efficiency of nanoparticles. Morphological analysis revealed structural alterations, including cell rounding and reduced cytoplasmic projections posttreatment. SLN-DTX and DTX induced damage to microtubules, binding proteins, and core fragmentation, impairing cell adhesion and proliferation. They also showed changes in analyses involving cellular organelles (mitochondria and lysosomes) and cellular metabolism. SLN-BLANK did not show significant toxicity in the AGS tumor lineage in any assays, behaving similarly to the untreated control. Association of docetaxel with solid lipid nanoparticles (SLN-DTX) demonstrates significant efficiency in inducing cytotoxic effects in gastric adenocarcinoma cells, since this formulation exhibited potent antitumor activity. Treatment with nanostructured docetaxel caused morphological and metabolic changes in addition to altering the release of molecules relevant to tumor progression. These findings support the potential use of SLN-DTX as a promising drug delivery system, offering an innovative and effective approach for gastric cancer treatment while potentially reducing the side effects associated with conventional therapies.

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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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