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Role of Folic Acid in the Therapeutic Action of Nanostructured Porous Silica Functionalized with Organotin(IV) Compounds Against Different Cancer Cell Lines.
Pharmaceutics ( IF 5.4 ) Pub Date : 2020-06-03 , DOI: 10.3390/pharmaceutics12060512
Diana Díaz-García 1, 2 , Karla Montalbán-Hernández 1, 3 , Irene Mena-Palomo 1, 3 , Patriciu Achimas-Cadariu 4, 5 , Antonio Rodríguez-Diéguez 6 , Eduardo López-Collazo 3 , Sanjiv Prashar 1 , Karina Ovejero Paredes 7, 8 , Marco Filice 7, 8 , Eva Fischer-Fodor 2, 9 , Santiago Gómez-Ruiz 1
Affiliation  

The synthesis, characterization and cytotoxic activity against different cancer cell lines of various mesoporous silica-based materials containing folate targeting moieties and a cytotoxic fragment based on a triphenyltin(IV) derivative have been studied. Two different mesoporous nanostructured silica systems have been used: firstly, micronic silica particles of the MSU-2 type and, secondly, mesoporous silica nanoparticles (MSNs) of about 80 nm. Both series of materials have been characterized by different methods, such as powder X-ray diffraction, X-ray fluorescence, absorption spectroscopy and microscopy. In addition, these systems have been tested against four different cancer cell lines, namely, OVCAR-3, DLD-1, A2780 and A431, in order to observe if the size of the silica-based systems and the quantity of incorporated folic acid influence their cytotoxic action. The results show that the materials are more active when the quantity of folic acid is higher, especially in those cells that overexpress folate receptors such as OVCAR-3 and DLD-1. In addition, the study of the potential modulation of the soluble folate receptor alpha (FOLR1) by treatment with the synthesized materials has been carried out using OVCAR-3, DLD-1, A2780 and A431 tumour cell lines. The results show that a relatively high concentration of folic acid functionalization of the nanostructured silica together with the incorporation of the cytotoxic tin fragment leads to an increase in the quantity of the soluble FOLR1 secreted by the tumour cells. In addition, the studies reported here show that this increase of the soluble FOLR1 occurs presumably by cutting the glycosyl-phosphatidylinositol anchor of membrane FR-α and by the release of intracellular FR-α. This study validates the potential use of a combination of mesoporous silica materials co-functionalized with folate targeting molecules and an organotin(IV) drug as a strategy for the therapeutic treatment of several cancer cells overexpressing folate receptors.

中文翻译:

叶酸在有机锡(IV)化合物功能化的纳米结构多孔二氧化硅对不同癌细胞系的治疗作用中的作用。

已经研究了各种不同的介孔二氧化硅基材料的合成,表征和针对不同癌细胞系的细胞毒性活性,这些材料包含叶酸靶向部分和基于三苯基锡(IV)衍生物的细胞毒性片段。已经使用了两种不同的介孔纳米结构的二氧化硅体系:首先,MSU-2型的微米级二氧化硅颗粒,其次,约80 nm的介孔二氧化硅纳米颗粒(MSN)。两种材料都通过不同的方法进行了表征,例如粉末X射线衍射,X射线荧光,吸收光谱和显微镜。此外,这些系统已针对OVCAR-3,DLD-1,A2780和A431等四种不同的癌细胞系进行了测试,为了观察二氧化硅基体系的大小和叶酸的掺入量是否影响其细胞毒性作用。结果表明,当叶酸含量较高时,该材料更具活性,尤其是在那些过表达叶酸受体(例如OVCAR-3和DLD-1)的细胞中。另外,已经通过使用OVCAR-3,DLD-1,A2780和A431肿瘤细胞系进行了通过用合成材料处理来潜在调节可溶性叶酸受体α(FOLR1)的研究。结果表明,相对较高浓度的纳米结构二氧化硅叶酸官能化以及细胞毒性锡片段的掺入导致肿瘤细胞分泌的可溶性FOLR1数量增加。此外,此处报道的研究表明,可溶性FOLR1的这种增​​加大概是通过切割膜FR-α的糖基-磷脂酰肌醇锚和细胞内FR-α的释放而发生的。这项研究验证了与叶酸靶向分子共功能化的中孔二氧化硅材料与有机锡(IV)药物的组合作为治疗几种过表达叶酸受体的癌细胞的策略的潜在用途。
更新日期:2020-06-03
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