Journal
BIOMEDICINE & PHARMACOTHERAPY
Volume 155, Issue -, Pages -Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2022.113723
Keywords
Calcium phosphate nanoparticles; Euphorbia lathyris; Colon cancer; Esculetin; Euphorbetin
Funding
- Spanish Ministry of Science, Innovation and Universities
- European Union [PTQ-17-09172, RTC-2017-6540-1, RTI2018-100934-B-I00, RTC2019-006870-1, RYC2016-21042]
- Junta de Andalucia FEDER program [P18-TP-1420, A-CTS666-UGR20, B-CTS-122-UGR20, P18-HO-3882, P18-TP-0969]
- Andalusian Government [AGR145, FQM-368, CTS-107]
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Functionalized amorphous calcium phosphate nanoparticles (ACP NPs) loaded with natural products (esculetin and euphorbetin) showed high selective cytotoxicity against colorectal cancer cells and significant reduction in tumor volume, size, and invasion in vivo. Treatment also increased beneficial bacterial population by restoring antioxidant systems in the colon mucosa of mice.
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 mu g/ml) compared to non-tumor (CCD18) cells (IC50, 420.77 mu g/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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