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载多西他赛固体脂质纳米粒(SLN-DTX)对胃腺癌的体外细胞毒性增强作用

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

作者信息

Vaz-Costa Laís, Radicchi Marina Arantes, Kauffmann Caterynne Melo, Tonelli Guilherme Sirimarco de Souza Silveira, Santos Igor Oliveira, Magalhães Kelly Grace, Báo Sônia Nair

机构信息

Graduate Program in Biological Sciences (Molecular Biology), Department of Cell Biology, Institute of Biological Sciences, University of Brasilia, Brasília, Brazil.

Laboratory of Microscopy and Microanalysis, Institute of Biological Sciences, University of Brasilia, Brasília, Brazil.

出版信息

J Biochem Mol Toxicol. 2025 Sep;39(9):e70456. doi: 10.1002/jbt.70456.

Abstract

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.

摘要

胃癌是全球主要的致死原因之一。尽管癌症治疗最近取得了进展,但胃癌患者的治愈率和生存率几乎没有变化。使用多西他赛等传统化疗药物受到一些缺点的限制,如脱发和血液毒性。本研究聚焦于载有多西他赛的固体脂质纳米粒(SLN-DTX)对胃腺癌细胞的抗肿瘤作用。SLN-DTX对癌细胞(AGS)显示出细胞毒性,在治疗24小时后,其半数抑制浓度(IC50)值低于游离多西他赛的浓度,证明了纳米粒的有效性。形态学分析揭示了结构改变,包括处理后细胞变圆和细胞质突起减少。SLN-DTX和多西他赛诱导微管、结合蛋白和核碎裂损伤,损害细胞黏附和增殖。它们在涉及细胞器(线粒体和溶酶体)和细胞代谢的分析中也显示出变化。SLN-BLANK在任何检测中对AGS肿瘤细胞系均未显示出显著毒性,其表现与未处理的对照组相似。多西他赛与固体脂质纳米粒结合(SLN-DTX)在诱导胃腺癌细胞的细胞毒性作用方面显示出显著效果,因为这种制剂表现出强大的抗肿瘤活性。用纳米结构的多西他赛治疗除了改变与肿瘤进展相关分子的释放外,还引起形态和代谢变化。这些发现支持将SLN-DTX作为一种有前景的药物递送系统的潜在用途,为胃癌治疗提供了一种创新且有效的方法,同时可能减少与传统疗法相关的副作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5c2/12369453/3c788f3d384a/JBT-39-e70456-g006.jpg

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