Liposomal encapsulation of cholecalciferol mitigates in vivo toxicity and delays tumor growth
IntroductionVitamin D3 (cholecalciferol) has demonstrated potential anticancer properties, but its clinical application is limited by associated toxicity at effective doses. This study investigated the use of liposomal encapsulation to increase the therapeutic efficacy of vitamin D3 while mitigating...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-01-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1529007/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832585039981838336 |
|---|---|
| author | Miriam Ezcurra-Hualde Miriam Ezcurra-Hualde Sara Zalba Sara Zalba Ángela Bella Ángela Bella Leire Arrizabalaga Leire Arrizabalaga Aline Risson Aline Risson Román García-Fuentes Román García-Fuentes Celia Gomar Celia Gomar Nuria Ardaiz Nuria Ardaiz Virginia Belsue Virginia Belsue David Ruiz-Guillamon David Ruiz-Guillamon Alejandro Serrano-Alcaide Alejandro Serrano-Alcaide Ainara Salgado Ainara Salgado Fernando Aranda Fernando Aranda Maria J. Garrido Maria J. Garrido Pedro Berraondo Pedro Berraondo Pedro Berraondo |
| author_facet | Miriam Ezcurra-Hualde Miriam Ezcurra-Hualde Sara Zalba Sara Zalba Ángela Bella Ángela Bella Leire Arrizabalaga Leire Arrizabalaga Aline Risson Aline Risson Román García-Fuentes Román García-Fuentes Celia Gomar Celia Gomar Nuria Ardaiz Nuria Ardaiz Virginia Belsue Virginia Belsue David Ruiz-Guillamon David Ruiz-Guillamon Alejandro Serrano-Alcaide Alejandro Serrano-Alcaide Ainara Salgado Ainara Salgado Fernando Aranda Fernando Aranda Maria J. Garrido Maria J. Garrido Pedro Berraondo Pedro Berraondo Pedro Berraondo |
| author_sort | Miriam Ezcurra-Hualde |
| collection | DOAJ |
| description | IntroductionVitamin D3 (cholecalciferol) has demonstrated potential anticancer properties, but its clinical application is limited by associated toxicity at effective doses. This study investigated the use of liposomal encapsulation to increase the therapeutic efficacy of vitamin D3 while mitigating its toxicity.MethodsLiposomal vitamin D3 (VD-LP) was prepared via the film-hydration method and characterized for particle size, polydispersity index, encapsulation efficiency, and long-term stability. In vitro gene expression modulation was evaluated in monocytic THP-1 cells, and antiproliferative effects were assessed in HT29 (colorectal), BT474 (breast), and TRAMP-C1 (prostate) cancer cell lines. In vivo antitumor efficacy and toxicity were tested in a mouse model with subcutaneously implanted MC38 tumors. Tumor growth, survival rates, and serum calcium and phosphate levels were analyzed.ResultsVD-LP demonstrated high encapsulation efficiency and stability over 90 days, with a consistent particle size of approximately 83 nm. VD-LP modulated immune-related and metabolic gene expression in THP-1 cells, including upregulation of antimicrobial peptides and vitamin D receptor genes. VD-LP showed superior antiproliferative effects compared to free vitamin D3 in all tested cancer cell lines. In vivo, VD-LP delayed tumor growth and improved survival without causing hypercalcemia, highlighting its favorable toxicity profile.DiscussionLiposomal encapsulation of vitamin D3 significantly improves its anticancer efficacy while mitigating toxicity, making it a promising strategy for future cancer therapies. VD-LP shows potential for enhanced therapeutic applications with reduced adverse effects, warranting further clinical exploration. |
| format | Article |
| id | doaj-art-fcd39e00ac9e4cb98194458a969da133 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-fcd39e00ac9e4cb98194458a969da1332025-01-27T06:40:32ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011610.3389/fimmu.2025.15290071529007Liposomal encapsulation of cholecalciferol mitigates in vivo toxicity and delays tumor growthMiriam Ezcurra-Hualde0Miriam Ezcurra-Hualde1Sara Zalba2Sara Zalba3Ángela Bella4Ángela Bella5Leire Arrizabalaga6Leire Arrizabalaga7Aline Risson8Aline Risson9Román García-Fuentes10Román García-Fuentes11Celia Gomar12Celia Gomar13Nuria Ardaiz14Nuria Ardaiz15Virginia Belsue16Virginia Belsue17David Ruiz-Guillamon18David Ruiz-Guillamon19Alejandro Serrano-Alcaide20Alejandro Serrano-Alcaide21Ainara Salgado22Ainara Salgado23Fernando Aranda24Fernando Aranda25Maria J. Garrido26Maria J. Garrido27Pedro Berraondo28Pedro Berraondo29Pedro Berraondo30Program of Immunology and Immunotherapy, Cima Universidad de Navarra, Cancer Center Clínica Universidad de Navarra (CCUN), Pamplona, SpainNavarra Institute for Health Research (IDISNA), Pamplona, SpainNavarra Institute for Health Research (IDISNA), Pamplona, SpainDepartment of Pharmaceutical Sciences, School of Pharmacy & Nutrition, University of Navarra, Pamplona, SpainProgram of Immunology and Immunotherapy, Cima Universidad de Navarra, Cancer Center Clínica Universidad de Navarra (CCUN), Pamplona, SpainNavarra Institute for Health Research (IDISNA), Pamplona, SpainProgram of Immunology and Immunotherapy, Cima Universidad de Navarra, Cancer Center Clínica Universidad de Navarra (CCUN), Pamplona, SpainNavarra Institute for Health Research (IDISNA), Pamplona, SpainProgram of Immunology and Immunotherapy, Cima Universidad de Navarra, Cancer Center Clínica Universidad de Navarra (CCUN), Pamplona, SpainNavarra Institute for Health Research (IDISNA), Pamplona, SpainProgram of Immunology and Immunotherapy, Cima Universidad de Navarra, Cancer Center Clínica Universidad de Navarra (CCUN), Pamplona, SpainNavarra Institute for Health Research (IDISNA), Pamplona, SpainProgram of Immunology and Immunotherapy, Cima Universidad de Navarra, Cancer Center Clínica Universidad de Navarra (CCUN), Pamplona, SpainNavarra Institute for Health Research (IDISNA), Pamplona, SpainProgram of Immunology and Immunotherapy, Cima Universidad de Navarra, Cancer Center Clínica Universidad de Navarra (CCUN), Pamplona, SpainNavarra Institute for Health Research (IDISNA), Pamplona, SpainProgram of Immunology and Immunotherapy, Cima Universidad de Navarra, Cancer Center Clínica Universidad de Navarra (CCUN), Pamplona, SpainNavarra Institute for Health Research (IDISNA), Pamplona, SpainProgram of Immunology and Immunotherapy, Cima Universidad de Navarra, Cancer Center Clínica Universidad de Navarra (CCUN), Pamplona, SpainNavarra Institute for Health Research (IDISNA), Pamplona, SpainNavarra Institute for Health Research (IDISNA), Pamplona, SpainDepartment of Pharmaceutical Sciences, School of Pharmacy & Nutrition, University of Navarra, Pamplona, SpainNavarra Institute for Health Research (IDISNA), Pamplona, SpainDepartment of Pharmaceutical Sciences, School of Pharmacy & Nutrition, University of Navarra, Pamplona, SpainProgram of Immunology and Immunotherapy, Cima Universidad de Navarra, Cancer Center Clínica Universidad de Navarra (CCUN), Pamplona, SpainNavarra Institute for Health Research (IDISNA), Pamplona, SpainNavarra Institute for Health Research (IDISNA), Pamplona, SpainDepartment of Pharmaceutical Sciences, School of Pharmacy & Nutrition, University of Navarra, Pamplona, SpainProgram of Immunology and Immunotherapy, Cima Universidad de Navarra, Cancer Center Clínica Universidad de Navarra (CCUN), Pamplona, SpainNavarra Institute for Health Research (IDISNA), Pamplona, SpainSpanish Center for Biomedical Research Network in Oncology (CIBERONC), Madrid, SpainIntroductionVitamin D3 (cholecalciferol) has demonstrated potential anticancer properties, but its clinical application is limited by associated toxicity at effective doses. This study investigated the use of liposomal encapsulation to increase the therapeutic efficacy of vitamin D3 while mitigating its toxicity.MethodsLiposomal vitamin D3 (VD-LP) was prepared via the film-hydration method and characterized for particle size, polydispersity index, encapsulation efficiency, and long-term stability. In vitro gene expression modulation was evaluated in monocytic THP-1 cells, and antiproliferative effects were assessed in HT29 (colorectal), BT474 (breast), and TRAMP-C1 (prostate) cancer cell lines. In vivo antitumor efficacy and toxicity were tested in a mouse model with subcutaneously implanted MC38 tumors. Tumor growth, survival rates, and serum calcium and phosphate levels were analyzed.ResultsVD-LP demonstrated high encapsulation efficiency and stability over 90 days, with a consistent particle size of approximately 83 nm. VD-LP modulated immune-related and metabolic gene expression in THP-1 cells, including upregulation of antimicrobial peptides and vitamin D receptor genes. VD-LP showed superior antiproliferative effects compared to free vitamin D3 in all tested cancer cell lines. In vivo, VD-LP delayed tumor growth and improved survival without causing hypercalcemia, highlighting its favorable toxicity profile.DiscussionLiposomal encapsulation of vitamin D3 significantly improves its anticancer efficacy while mitigating toxicity, making it a promising strategy for future cancer therapies. VD-LP shows potential for enhanced therapeutic applications with reduced adverse effects, warranting further clinical exploration.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1529007/fullliposomal encapsulationvitamin D3anticancer efficacygene expressiontumor growth |
| spellingShingle | Miriam Ezcurra-Hualde Miriam Ezcurra-Hualde Sara Zalba Sara Zalba Ángela Bella Ángela Bella Leire Arrizabalaga Leire Arrizabalaga Aline Risson Aline Risson Román García-Fuentes Román García-Fuentes Celia Gomar Celia Gomar Nuria Ardaiz Nuria Ardaiz Virginia Belsue Virginia Belsue David Ruiz-Guillamon David Ruiz-Guillamon Alejandro Serrano-Alcaide Alejandro Serrano-Alcaide Ainara Salgado Ainara Salgado Fernando Aranda Fernando Aranda Maria J. Garrido Maria J. Garrido Pedro Berraondo Pedro Berraondo Pedro Berraondo Liposomal encapsulation of cholecalciferol mitigates in vivo toxicity and delays tumor growth Frontiers in Immunology liposomal encapsulation vitamin D3 anticancer efficacy gene expression tumor growth |
| title | Liposomal encapsulation of cholecalciferol mitigates in vivo toxicity and delays tumor growth |
| title_full | Liposomal encapsulation of cholecalciferol mitigates in vivo toxicity and delays tumor growth |
| title_fullStr | Liposomal encapsulation of cholecalciferol mitigates in vivo toxicity and delays tumor growth |
| title_full_unstemmed | Liposomal encapsulation of cholecalciferol mitigates in vivo toxicity and delays tumor growth |
| title_short | Liposomal encapsulation of cholecalciferol mitigates in vivo toxicity and delays tumor growth |
| title_sort | liposomal encapsulation of cholecalciferol mitigates in vivo toxicity and delays tumor growth |
| topic | liposomal encapsulation vitamin D3 anticancer efficacy gene expression tumor growth |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1529007/full |
| work_keys_str_mv | AT miriamezcurrahualde liposomalencapsulationofcholecalciferolmitigatesinvivotoxicityanddelaystumorgrowth AT miriamezcurrahualde liposomalencapsulationofcholecalciferolmitigatesinvivotoxicityanddelaystumorgrowth AT sarazalba liposomalencapsulationofcholecalciferolmitigatesinvivotoxicityanddelaystumorgrowth AT sarazalba liposomalencapsulationofcholecalciferolmitigatesinvivotoxicityanddelaystumorgrowth AT angelabella liposomalencapsulationofcholecalciferolmitigatesinvivotoxicityanddelaystumorgrowth AT angelabella liposomalencapsulationofcholecalciferolmitigatesinvivotoxicityanddelaystumorgrowth AT leirearrizabalaga liposomalencapsulationofcholecalciferolmitigatesinvivotoxicityanddelaystumorgrowth AT leirearrizabalaga liposomalencapsulationofcholecalciferolmitigatesinvivotoxicityanddelaystumorgrowth AT alinerisson liposomalencapsulationofcholecalciferolmitigatesinvivotoxicityanddelaystumorgrowth AT alinerisson liposomalencapsulationofcholecalciferolmitigatesinvivotoxicityanddelaystumorgrowth AT romangarciafuentes liposomalencapsulationofcholecalciferolmitigatesinvivotoxicityanddelaystumorgrowth AT romangarciafuentes liposomalencapsulationofcholecalciferolmitigatesinvivotoxicityanddelaystumorgrowth AT celiagomar liposomalencapsulationofcholecalciferolmitigatesinvivotoxicityanddelaystumorgrowth AT celiagomar liposomalencapsulationofcholecalciferolmitigatesinvivotoxicityanddelaystumorgrowth AT nuriaardaiz liposomalencapsulationofcholecalciferolmitigatesinvivotoxicityanddelaystumorgrowth AT nuriaardaiz liposomalencapsulationofcholecalciferolmitigatesinvivotoxicityanddelaystumorgrowth AT virginiabelsue liposomalencapsulationofcholecalciferolmitigatesinvivotoxicityanddelaystumorgrowth AT virginiabelsue liposomalencapsulationofcholecalciferolmitigatesinvivotoxicityanddelaystumorgrowth AT davidruizguillamon liposomalencapsulationofcholecalciferolmitigatesinvivotoxicityanddelaystumorgrowth AT davidruizguillamon liposomalencapsulationofcholecalciferolmitigatesinvivotoxicityanddelaystumorgrowth AT alejandroserranoalcaide liposomalencapsulationofcholecalciferolmitigatesinvivotoxicityanddelaystumorgrowth AT alejandroserranoalcaide liposomalencapsulationofcholecalciferolmitigatesinvivotoxicityanddelaystumorgrowth AT ainarasalgado liposomalencapsulationofcholecalciferolmitigatesinvivotoxicityanddelaystumorgrowth AT ainarasalgado liposomalencapsulationofcholecalciferolmitigatesinvivotoxicityanddelaystumorgrowth AT fernandoaranda liposomalencapsulationofcholecalciferolmitigatesinvivotoxicityanddelaystumorgrowth AT fernandoaranda liposomalencapsulationofcholecalciferolmitigatesinvivotoxicityanddelaystumorgrowth AT mariajgarrido liposomalencapsulationofcholecalciferolmitigatesinvivotoxicityanddelaystumorgrowth AT mariajgarrido liposomalencapsulationofcholecalciferolmitigatesinvivotoxicityanddelaystumorgrowth AT pedroberraondo liposomalencapsulationofcholecalciferolmitigatesinvivotoxicityanddelaystumorgrowth AT pedroberraondo liposomalencapsulationofcholecalciferolmitigatesinvivotoxicityanddelaystumorgrowth AT pedroberraondo liposomalencapsulationofcholecalciferolmitigatesinvivotoxicityanddelaystumorgrowth |