Laís Vaz-Costa, Marina Arantes Radicchi, Caterynne Melo Kauffmann, Guilherme Sirimarco de Souza Silveira Tonelli, Igor Oliveira Santos, Kelly Grace Magalhães, Sônia Nair Báo
{"title":"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","authors":"Laís Vaz-Costa, Marina Arantes Radicchi, Caterynne Melo Kauffmann, Guilherme Sirimarco de Souza Silveira Tonelli, Igor Oliveira Santos, Kelly Grace Magalhães, Sônia Nair Báo","doi":"10.1002/jbt.70456","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n <p>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.</p>\n </section>\n </div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8000,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70456","citationCount":"0","resultStr":"{\"title\":\"Enhanced Cytotoxic Effects of Docetaxel-Loaded Solid Lipid Nanoparticles (SLN-DTX) on Gastric Adenocarcinoma In Vitro\",\"authors\":\"Laís Vaz-Costa, Marina Arantes Radicchi, Caterynne Melo Kauffmann, Guilherme Sirimarco de Souza Silveira Tonelli, Igor Oliveira Santos, Kelly Grace Magalhães, Sônia Nair Báo\",\"doi\":\"10.1002/jbt.70456\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n <p>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.</p>\\n </section>\\n </div>\",\"PeriodicalId\":15151,\"journal\":{\"name\":\"Journal of Biochemical and Molecular Toxicology\",\"volume\":\"39 9\",\"pages\":\"\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2025-08-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70456\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Biochemical and Molecular Toxicology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/jbt.70456\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Biochemical and Molecular Toxicology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jbt.70456","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
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.
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.