Díaz-García Diana, Montalbán-Hernández Karla, Mena-Palomo Irene, Achimas-Cadariu Patriciu, Rodríguez-Diéguez Antonio, López-Collazo Eduardo, Prashar Sanjiv, Ovejero Paredes Karina, Filice Marco, Fischer-Fodor Eva, Gómez-Ruiz Santiago
COMET-NANO Group, Departamento de Biología y Geología, Física y Química Inorgánica, ESCET, Universidad Rey Juan Carlos, 28933, Móstoles, Spain.
Tumour Biology Department, the Institute of Oncology "Prof. Dr. I. Chiricuta", RO-400015 Cluj-Napoca, Romania.
Pharmaceutics. 2020 Jun 3;12(6):512. doi: 10.3390/pharmaceutics12060512.
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.
对含有叶酸靶向部分和基于三苯基锡（IV）衍生物的细胞毒性片段的各种介孔二氧化硅基材料的合成、表征及其对不同癌细胞系的细胞毒性活性进行了研究。使用了两种不同的介孔纳米结构二氧化硅体系：首先是MSU - 2型微米级二氧化硅颗粒，其次是约80 nm的介孔二氧化硅纳米颗粒（MSN）。这两个系列的材料都通过不同方法进行了表征，如粉末X射线衍射、X射线荧光、吸收光谱和显微镜检查。此外，这些体系针对四种不同的癌细胞系，即OVCAR - 3、DLD - 1、A2780和A431进行了测试，以观察基于二氧化硅体系的尺寸和掺入叶酸的量是否会影响它们的细胞毒性作用。结果表明，当叶酸量较高时，材料的活性更高，特别是在那些过表达叶酸受体的细胞中，如OVCAR - 3和DLD - 1。此外，使用OVCAR - 3、DLD - 1、A2780和A431肿瘤细胞系对合成材料处理后可溶性叶酸受体α（FOLR1）的潜在调节进行了研究。结果表明，纳米结构二氧化硅的相对高浓度叶酸功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量增加。此外，此处报道的研究表明，可溶性FOLR1的这种增加可能是通过切割膜FR - α的糖基磷脂酰肌醇锚并释放细胞内FR - α而发生的。本研究验证了将与叶酸靶向分子共功能化的介孔二氧化硅材料和有机锡（IV）药物组合作为治疗几种过表达叶酸受体癌细胞的策略的潜在用途。
