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.

无定形磷酸钙纳米粒子（ACP NPs）表现出优异的生物相容性和生物降解性。用从Euphorbia lathyris 中提取的两种香豆素化合物（七叶素和大戟黄素）对 ACP NP 进行功能化种子（BC-ACP NPs）显示出高负载能力（分别为 0.03% 和 0.34% (w/w) 的七叶苷和大戟素）和吸附效率（分别为 2.6% 和 33.5%）。BC-ACP NPs 对人体血细胞无毒，与非肿瘤 (CCD18) 细胞 (IC50, 420.77 微克/毫升）。碳酸酐酶的抑制和自噬性细胞死亡似乎都参与了它们的作用机制。有趣的是，使用两种不同的 CRC 诱导模型用 BC-ACP NPs 进行体内治疗显示肿瘤体积显着减少 (62%)，息肉的数量和大小显着减少。还观察到肿瘤脉管系统发育不良和正常组织侵袭。而且，治疗通过恢复小鼠结肠粘膜中的抗氧化系统来增加阿克曼氏菌的细菌数量。这些结果表明，基于负载天然产物的仿生磷酸钙 NPs 设计针对 CRC 的创新和更有效的疗法是一条有希望的途径。