Sphingomyelin nanosystems loaded with uroguanylin and etoposide for treating metastatic colorectal cancer
Abstract Colorectal cancer is the third most frequently diagnosed cancer malignancy and the second leading cause of cancer-related deaths worldwide. Therefore, it is of utmost importance to provide new therapeutic options that can improve survival. Sphingomyelin nanosystems (SNs) are a promising typ...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-96578-z |
| _version_ | 1818841983743950848 |
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| author | Belén L. Bouzo Saínza Lores Raneem Jatal Sandra Alijas María José Alonso Inmaculada Conejos-Sánchez María de la Fuente |
| author_facet | Belén L. Bouzo Saínza Lores Raneem Jatal Sandra Alijas María José Alonso Inmaculada Conejos-Sánchez María de la Fuente |
| author_sort | Belén L. Bouzo |
| collection | DOAJ |
| description | Abstract Colorectal cancer is the third most frequently diagnosed cancer malignancy and the second leading cause of cancer-related deaths worldwide. Therefore, it is of utmost importance to provide new therapeutic options that can improve survival. Sphingomyelin nanosystems (SNs) are a promising type of nanocarriers with potential for association of different types of drugs and, thus, for the development of combination treatments. In this work we propose the chemical modification of uroguanylin, a natural ligand for the Guanylyl Cyclase (GCC) receptor, expressed in metastatic colorectal cancer tumors, to favour its anchoring to SNs (UroGm-SNs). The anti-cancer drug etoposide (Etp) was additionally encapsulated for the development of a combination strategy (UroGm-Etp-SNs). Results from in vitro studies showed that UroGm-Etp-SNs can interact with colorectal cancer cells that express the GCC receptor and mediate an antiproliferative response, which is more remarkable for the drugs in combination. The potential of UroGm-Etp-SNs to treat metastatic colorectal cancer cells was complemented with an in vivo experiment in a xenograft mice model. |
| first_indexed | 2024-12-19T04:34:45Z |
| format | Article |
| id | doaj.art-63332139058d49b2bcb04ce39b117206 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-19T04:34:45Z |
| publishDate | 2021-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-63332139058d49b2bcb04ce39b1172062022-12-21T20:35:47ZengNature PortfolioScientific Reports2045-23222021-08-0111111210.1038/s41598-021-96578-zSphingomyelin nanosystems loaded with uroguanylin and etoposide for treating metastatic colorectal cancerBelén L. Bouzo0Saínza Lores1Raneem Jatal2Sandra Alijas3María José Alonso4Inmaculada Conejos-Sánchez5María de la Fuente6Nano-Oncology and Translational Therapeutics Unit, Health Research Institute of Santiago de Compostela (IDIS), SERGAS, CIBERONCNano-Oncology and Translational Therapeutics Unit, Health Research Institute of Santiago de Compostela (IDIS), SERGAS, CIBERONCNano-Oncology and Translational Therapeutics Unit, Health Research Institute of Santiago de Compostela (IDIS), SERGAS, CIBERONCNano-Oncology and Translational Therapeutics Unit, Health Research Institute of Santiago de Compostela (IDIS), SERGAS, CIBERONCCentre for Research in Molecular Medicine and Chronic Diseases (CIMUS), University of Santiago de Compostela (USC)Centre for Research in Molecular Medicine and Chronic Diseases (CIMUS), University of Santiago de Compostela (USC)Nano-Oncology and Translational Therapeutics Unit, Health Research Institute of Santiago de Compostela (IDIS), SERGAS, CIBERONCAbstract Colorectal cancer is the third most frequently diagnosed cancer malignancy and the second leading cause of cancer-related deaths worldwide. Therefore, it is of utmost importance to provide new therapeutic options that can improve survival. Sphingomyelin nanosystems (SNs) are a promising type of nanocarriers with potential for association of different types of drugs and, thus, for the development of combination treatments. In this work we propose the chemical modification of uroguanylin, a natural ligand for the Guanylyl Cyclase (GCC) receptor, expressed in metastatic colorectal cancer tumors, to favour its anchoring to SNs (UroGm-SNs). The anti-cancer drug etoposide (Etp) was additionally encapsulated for the development of a combination strategy (UroGm-Etp-SNs). Results from in vitro studies showed that UroGm-Etp-SNs can interact with colorectal cancer cells that express the GCC receptor and mediate an antiproliferative response, which is more remarkable for the drugs in combination. The potential of UroGm-Etp-SNs to treat metastatic colorectal cancer cells was complemented with an in vivo experiment in a xenograft mice model.https://doi.org/10.1038/s41598-021-96578-z |
| spellingShingle | Belén L. Bouzo Saínza Lores Raneem Jatal Sandra Alijas María José Alonso Inmaculada Conejos-Sánchez María de la Fuente Sphingomyelin nanosystems loaded with uroguanylin and etoposide for treating metastatic colorectal cancer Scientific Reports |
| title | Sphingomyelin nanosystems loaded with uroguanylin and etoposide for treating metastatic colorectal cancer |
| title_full | Sphingomyelin nanosystems loaded with uroguanylin and etoposide for treating metastatic colorectal cancer |
| title_fullStr | Sphingomyelin nanosystems loaded with uroguanylin and etoposide for treating metastatic colorectal cancer |
| title_full_unstemmed | Sphingomyelin nanosystems loaded with uroguanylin and etoposide for treating metastatic colorectal cancer |
| title_short | Sphingomyelin nanosystems loaded with uroguanylin and etoposide for treating metastatic colorectal cancer |
| title_sort | sphingomyelin nanosystems loaded with uroguanylin and etoposide for treating metastatic colorectal cancer |
| url | https://doi.org/10.1038/s41598-021-96578-z |
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