RT Journal Article T1 Colon cancer therapy with calcium phosphate nanoparticles loading bioactive compounds from Euphorbia lathyris: In vitro and in vivo assay. A1 Mesas, Cristina A1 Garces, Victor A1 Martinez, Rosario A1 Ortiz, Raul A1 Doello, Kevin A1 Dominguez-Vera, Jose M A1 Bermudez, Francisco A1 Porres, Jesus M A1 Lopez-Jurado, Maria A1 Melguizo, Consolacion A1 Delgado-Lopez, Jose M A1 Prados, Jose K1 Calcium phosphate nanoparticles K1 Colon cancer K1 Esculetin K1 Euphorbetin K1 Euphorbia lathyris AB 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. PB Elsevier Masson YR 2022 FD 2022-09-19 LK http://hdl.handle.net/10668/22052 UL http://hdl.handle.net/10668/22052 LA en NO Mesas C, Garcés V, Martínez R, Ortiz R, Doello K, Dominguez-Vera JM, et al. Colon cancer therapy with calcium phosphate nanoparticles loading bioactive compounds from Euphorbia lathyris: In vitro and in vivo assay. Biomed Pharmacother. 2022 Nov;155:113723. NO This research was funded by the Spanish Ministry of Science, Innovation and Universities as well as the European Union (PTQ-17-09172, RTC-2017-6540-1, RTI2018-100934-B-I00, RTC2019-006870-1, RYC-2016-21042) and in part by Junta de Andalucía (P18-TP-1420, A-CTS-666-UGR20, B-CTS-122-UGR20, P18-HO-3882 and P18-TP-0969) FEDER program. In addition, this work was supported by funds from research groups AGR145, FQM-368 and CTS-107 (Andalusian Government). The authors would like to thank technical assistance from the Centro de Instrumentación Científica (CIC) (Granada University) and Antonio Murillo Cancho from the University of Almería and CELLBITEC S.L. All animal experiments were conducted under the Ethical and Regulatory Guidelines for Animal Experiments defined by the University of Granada (Certificate number: 16/01/2020/005). DS RISalud RD Apr 7, 2025