Role of Folic Acid in the Therapeutic Action of Nanostructured Porous Silica Functionalized with Organotin(IV) Compounds against Different Cancer Cell Lines
Metadata
Show full item recordEditorial
MDPI
Materia
Tin Anticancer Mesoporous silica Folic acid Cytotoxicity FOLR1
Date
2020-06-03Referencia bibliográfica
Díaz-García, D., Montalbán-Hernández, K., Mena-Palomo, I., Achimas-Cadariu, P., Rodríguez-Diéguez, A., López-Collazo, E., ... & Gómez-Ruiz, S. (2020). Role of Folic Acid in the Therapeutic Action of Nanostructured Porous Silica Functionalized with Organotin (IV) Compounds Against Different Cancer Cell Lines. Pharmaceutics, 12(6), 512. [doi: 10.3390/pharmaceutics12060512]
Sponsorship
Spanish Government RTI2018-094322-B-I00 CTQ2017-90802-REDT; Ministry of Research and Innovation, CNCS-UEFISCDI within PNCDI III PN-III-P4-ID-PCCF-2016-0142Abstract
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.