Amanda Blanque Becceneri, Angelina Maria Fuzer, Ana Carolina Lopes, Patrícia Bento da Silva, Ana Maria Plutin, Alzir Azevedo Batista, Marlus Chorilli, Márcia Regina Cominetti
{"title":"钌复合物 Ru(ThySMet) 的纳米封装：提高二维和三维培养模型中乳腺肿瘤细胞选择性细胞毒性的策略。","authors":"Amanda Blanque Becceneri, Angelina Maria Fuzer, Ana Carolina Lopes, Patrícia Bento da Silva, Ana Maria Plutin, Alzir Azevedo Batista, Marlus Chorilli, Márcia Regina Cominetti","doi":"10.2174/1570163820666230606110457","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Ruthenium complexes have shown promise in treating many cancers, including breast cancer. Previous studies of our group have demonstrated the potential of the trans- [Ru(PPh3)2(N,N-dimethylN'-thiophenylthioureato-k2O,S)(bipy)]PF6 complex, the Ru(ThySMet), in the treatment of breast tumor cancers, both in 2D and 3D culture systems. Additionally, this complex presented low toxicity when tested <i>in vivo</i>.</p><p><strong>Aims: </strong>Improve the Ru(ThySMet) activity by incorporating the complex into a microemulsion (ME) and testing its <i>in vitro</i> effects.</p><p><strong>Methods: </strong>The ME-incorporated Ru(ThySMet) complex, Ru(ThySMet)<sub>ME</sub>, was tested for its biological effects in two- (2D) and three-dimensional (3D) cultures using different types of breast cells, MDAMB- 231, MCF-10A, 4T1.13ch5T1, HMT-3522 and Balb/C 3T3 fibroblasts.</p><p><strong>Results: </strong>An increased selective cytotoxicity of the Ru(ThySMet)<sub>ME</sub> for tumor cells was found in 2D cell culture, compared with the original complex. This novel compound also changed the shape of tumor cells and inhibited cell migration with more specificity. Additional 3D cell culture tests using the non-neoplastic S1 and the triple-negative invasive T4-2 breast cells have shown that Ru(ThySMet)<sub>ME</sub> presented increased selective cytotoxicity for tumor cells compared with the 2D results. The morphology assay performed in 3D also revealed its ability to reduce the size of the 3D structures and increase the circularity in T4-2 cells.</p><p><strong>Conclusion: </strong>These results demonstrate that the Ru(ThySMet)<sub>ME</sub> is a promising strategy to increase its solubility, delivery, and bioaccumulation in target breast tumors.</p>","PeriodicalId":10858,"journal":{"name":"Current drug discovery technologies","volume":" ","pages":"e060623217687"},"PeriodicalIF":0.0000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Nanoencapsulation of Ruthenium Complex Ru(ThySMet): A Strategy to Improve Selective Cytotoxicity against Breast Tumor Cells in 2D and 3D Culture Models.\",\"authors\":\"Amanda Blanque Becceneri, Angelina Maria Fuzer, Ana Carolina Lopes, Patrícia Bento da Silva, Ana Maria Plutin, Alzir Azevedo Batista, Marlus Chorilli, Márcia Regina Cominetti\",\"doi\":\"10.2174/1570163820666230606110457\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Ruthenium complexes have shown promise in treating many cancers, including breast cancer. Previous studies of our group have demonstrated the potential of the trans- [Ru(PPh3)2(N,N-dimethylN'-thiophenylthioureato-k2O,S)(bipy)]PF6 complex, the Ru(ThySMet), in the treatment of breast tumor cancers, both in 2D and 3D culture systems. Additionally, this complex presented low toxicity when tested <i>in vivo</i>.</p><p><strong>Aims: </strong>Improve the Ru(ThySMet) activity by incorporating the complex into a microemulsion (ME) and testing its <i>in vitro</i> effects.</p><p><strong>Methods: </strong>The ME-incorporated Ru(ThySMet) complex, Ru(ThySMet)<sub>ME</sub>, was tested for its biological effects in two- (2D) and three-dimensional (3D) cultures using different types of breast cells, MDAMB- 231, MCF-10A, 4T1.13ch5T1, HMT-3522 and Balb/C 3T3 fibroblasts.</p><p><strong>Results: </strong>An increased selective cytotoxicity of the Ru(ThySMet)<sub>ME</sub> for tumor cells was found in 2D cell culture, compared with the original complex. This novel compound also changed the shape of tumor cells and inhibited cell migration with more specificity. Additional 3D cell culture tests using the non-neoplastic S1 and the triple-negative invasive T4-2 breast cells have shown that Ru(ThySMet)<sub>ME</sub> presented increased selective cytotoxicity for tumor cells compared with the 2D results. The morphology assay performed in 3D also revealed its ability to reduce the size of the 3D structures and increase the circularity in T4-2 cells.</p><p><strong>Conclusion: </strong>These results demonstrate that the Ru(ThySMet)<sub>ME</sub> is a promising strategy to increase its solubility, delivery, and bioaccumulation in target breast tumors.</p>\",\"PeriodicalId\":10858,\"journal\":{\"name\":\"Current drug discovery technologies\",\"volume\":\" \",\"pages\":\"e060623217687\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current drug discovery technologies\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.2174/1570163820666230606110457\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"Pharmacology, Toxicology and Pharmaceutics\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current drug discovery technologies","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2174/1570163820666230606110457","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"Pharmacology, Toxicology and Pharmaceutics","Score":null,"Total":0}
Nanoencapsulation of Ruthenium Complex Ru(ThySMet): A Strategy to Improve Selective Cytotoxicity against Breast Tumor Cells in 2D and 3D Culture Models.
Background: Ruthenium complexes have shown promise in treating many cancers, including breast cancer. Previous studies of our group have demonstrated the potential of the trans- [Ru(PPh3)2(N,N-dimethylN'-thiophenylthioureato-k2O,S)(bipy)]PF6 complex, the Ru(ThySMet), in the treatment of breast tumor cancers, both in 2D and 3D culture systems. Additionally, this complex presented low toxicity when tested in vivo.
Aims: Improve the Ru(ThySMet) activity by incorporating the complex into a microemulsion (ME) and testing its in vitro effects.
Methods: The ME-incorporated Ru(ThySMet) complex, Ru(ThySMet)ME, was tested for its biological effects in two- (2D) and three-dimensional (3D) cultures using different types of breast cells, MDAMB- 231, MCF-10A, 4T1.13ch5T1, HMT-3522 and Balb/C 3T3 fibroblasts.
Results: An increased selective cytotoxicity of the Ru(ThySMet)ME for tumor cells was found in 2D cell culture, compared with the original complex. This novel compound also changed the shape of tumor cells and inhibited cell migration with more specificity. Additional 3D cell culture tests using the non-neoplastic S1 and the triple-negative invasive T4-2 breast cells have shown that Ru(ThySMet)ME presented increased selective cytotoxicity for tumor cells compared with the 2D results. The morphology assay performed in 3D also revealed its ability to reduce the size of the 3D structures and increase the circularity in T4-2 cells.
Conclusion: These results demonstrate that the Ru(ThySMet)ME is a promising strategy to increase its solubility, delivery, and bioaccumulation in target breast tumors.
期刊介绍：
Due to the plethora of new approaches being used in modern drug discovery by the pharmaceutical industry, Current Drug Discovery Technologies has been established to provide comprehensive overviews of all the major modern techniques and technologies used in drug design and discovery. The journal is the forum for publishing both original research papers and reviews describing novel approaches and cutting edge technologies used in all stages of drug discovery. The journal addresses the multidimensional challenges of drug discovery science including integration issues of the drug discovery process.
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