Colon cancer therapy with calcium phosphate nanoparticles loading bioactive compounds from Euphorbia lathyris: In vitro and in vivo assay

Amorphous calcium phosphate nanoparticles (ACP NPs) exhibit excellent biocompatibility and biodegradability properties. ACP NPs were functionalized with two coumarin compounds (esculetin and euphorbetin) extracted from Euphorbia lathyris seeds (BC-ACP NPs) showing high loading capacity (0.03% and 0....

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Main Authors: Cristina Mesas, Víctor Garcés, Rosario Martínez, Raúl Ortiz, Kevin Doello, Jose M. Dominguez-Vera, Francisco Bermúdez, Jesús M. Porres, María López-Jurado, Consolación Melguizo, José M. Delgado-López, Jose Prados
Format: Article
Language:English
Published: Elsevier 2022-11-01
Series:Biomedicine & Pharmacotherapy
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Online Access:http://www.sciencedirect.com/science/article/pii/S075333222201112X
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author Cristina Mesas
Víctor Garcés
Rosario Martínez
Raúl Ortiz
Kevin Doello
Jose M. Dominguez-Vera
Francisco Bermúdez
Jesús M. Porres
María López-Jurado
Consolación Melguizo
José M. Delgado-López
Jose Prados
author_facet Cristina Mesas
Víctor Garcés
Rosario Martínez
Raúl Ortiz
Kevin Doello
Jose M. Dominguez-Vera
Francisco Bermúdez
Jesús M. Porres
María López-Jurado
Consolación Melguizo
José M. Delgado-López
Jose Prados
author_sort Cristina Mesas
collection DOAJ
description Amorphous calcium phosphate nanoparticles (ACP NPs) exhibit excellent biocompatibility and biodegradability properties. ACP NPs were functionalized with two coumarin compounds (esculetin and euphorbetin) extracted from Euphorbia lathyris seeds (BC-ACP NPs) showing high loading capacity (0.03% and 0.34% (w/w) for esculetin and euphorbetin, respectively) and adsorption efficiency (2.6% and 33.5%, respectively). BC-ACP NPs, no toxic to human blood cells, showed a more selective cytotoxicity against colorectal cancer (CRC) cells (T-84 cells) (IC50, 71.42 µg/ml) compared to non-tumor (CCD18) cells (IC50, 420.77 µg/ml). Both, the inhibition of carbonic anhydrase and autophagic cell death appeared to be involved in their action mechanism. Interestingly, in vivo treatment with BC-ACPs NPs using two different models of CRC induction showed a significant reduction in tumor volume (62%) and a significant decrease in the number and size of polyps. A poor development of tumor vasculature and invasion of normal tissue were also observed. Moreover, treatment increased the bacterial population of Akkermansia by restoring antioxidant systems in the colonic mucosa of mice. These results show a promising pathway to design innovative and more efficient therapies against CRC based on biomimetic calcium phosphate NPs loaded with natural products.
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spelling doaj.art-93dbecab6e114e71ab36c0ca9d2092842022-12-22T04:36:49ZengElsevierBiomedicine & Pharmacotherapy0753-33222022-11-01155113723Colon cancer therapy with calcium phosphate nanoparticles loading bioactive compounds from Euphorbia lathyris: In vitro and in vivo assayCristina Mesas0Víctor Garcés1Rosario Martínez2Raúl Ortiz3Kevin Doello4Jose M. Dominguez-Vera5Francisco Bermúdez6Jesús M. Porres7María López-Jurado8Consolación Melguizo9José M. Delgado-López10Jose Prados11Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, 18100 Granada, Spain; Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, 18071 Granada, Spain; Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18014 Granada, SpainDepartment of Inorganic Chemistry, Faculty of Science, University of Granada, 18071 Granada, SpainDepartment of Physiology, Institute of Nutrition and Food Technology (INyTA), Center of Biomedical Research (CIBM), University of Granada, 18100 Granada, SpainInstitute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, 18100 Granada, Spain; Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, 18071 Granada, Spain; Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18014 Granada, SpainMedical Oncology Service, Virgen de las Nieves Hospital, 18014 Granada, SpainDepartment of Inorganic Chemistry, Faculty of Science, University of Granada, 18071 Granada, SpainCellbitec S.L., N.I.F. B04847216, Scientific Headquarters of the Almería Technology Park, Universidad de Almería, La Cañada, 04128 Almería, SpainDepartment of Physiology, Institute of Nutrition and Food Technology (INyTA), Center of Biomedical Research (CIBM), University of Granada, 18100 Granada, SpainDepartment of Physiology, Institute of Nutrition and Food Technology (INyTA), Center of Biomedical Research (CIBM), University of Granada, 18100 Granada, SpainInstitute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, 18100 Granada, Spain; Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, 18071 Granada, Spain; Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18014 Granada, Spain; Corresponding author at: Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, 18100 Granada, Spain.Department of Inorganic Chemistry, Faculty of Science, University of Granada, 18071 Granada, SpainInstitute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, 18100 Granada, Spain; Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, 18071 Granada, Spain; Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18014 Granada, SpainAmorphous calcium phosphate nanoparticles (ACP NPs) exhibit excellent biocompatibility and biodegradability properties. ACP NPs were functionalized with two coumarin compounds (esculetin and euphorbetin) extracted from Euphorbia lathyris seeds (BC-ACP NPs) showing high loading capacity (0.03% and 0.34% (w/w) for esculetin and euphorbetin, respectively) and adsorption efficiency (2.6% and 33.5%, respectively). BC-ACP NPs, no toxic to human blood cells, showed a more selective cytotoxicity against colorectal cancer (CRC) cells (T-84 cells) (IC50, 71.42 µg/ml) compared to non-tumor (CCD18) cells (IC50, 420.77 µg/ml). Both, the inhibition of carbonic anhydrase and autophagic cell death appeared to be involved in their action mechanism. Interestingly, in vivo treatment with BC-ACPs NPs using two different models of CRC induction showed a significant reduction in tumor volume (62%) and a significant decrease in the number and size of polyps. A poor development of tumor vasculature and invasion of normal tissue were also observed. Moreover, treatment increased the bacterial population of Akkermansia by restoring antioxidant systems in the colonic mucosa of mice. These results show a promising pathway to design innovative and more efficient therapies against CRC based on biomimetic calcium phosphate NPs loaded with natural products.http://www.sciencedirect.com/science/article/pii/S075333222201112XCalcium phosphate nanoparticlesEuphorbia lathyrisColon cancerEsculetinEuphorbetin
spellingShingle Cristina Mesas
Víctor Garcés
Rosario Martínez
Raúl Ortiz
Kevin Doello
Jose M. Dominguez-Vera
Francisco Bermúdez
Jesús M. Porres
María López-Jurado
Consolación Melguizo
José M. Delgado-López
Jose Prados
Colon cancer therapy with calcium phosphate nanoparticles loading bioactive compounds from Euphorbia lathyris: In vitro and in vivo assay
Biomedicine & Pharmacotherapy
Calcium phosphate nanoparticles
Euphorbia lathyris
Colon cancer
Esculetin
Euphorbetin
title Colon cancer therapy with calcium phosphate nanoparticles loading bioactive compounds from Euphorbia lathyris: In vitro and in vivo assay
title_full Colon cancer therapy with calcium phosphate nanoparticles loading bioactive compounds from Euphorbia lathyris: In vitro and in vivo assay
title_fullStr Colon cancer therapy with calcium phosphate nanoparticles loading bioactive compounds from Euphorbia lathyris: In vitro and in vivo assay
title_full_unstemmed Colon cancer therapy with calcium phosphate nanoparticles loading bioactive compounds from Euphorbia lathyris: In vitro and in vivo assay
title_short Colon cancer therapy with calcium phosphate nanoparticles loading bioactive compounds from Euphorbia lathyris: In vitro and in vivo assay
title_sort colon cancer therapy with calcium phosphate nanoparticles loading bioactive compounds from euphorbia lathyris in vitro and in vivo assay
topic Calcium phosphate nanoparticles
Euphorbia lathyris
Colon cancer
Esculetin
Euphorbetin
url http://www.sciencedirect.com/science/article/pii/S075333222201112X
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