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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

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Díaz-García, Diana and Montalbán-Hernández, Karla and Mena-Palomo, Irene and Achimas-Cadariu, Patriciu and Rodríguez Diéguez, Antonio and Eduardo, López-Collado and Prashar, Sanjiv and Ovejero Paredes, Karina and Filice, Marco and Fischer-Fodor, Eva and Gómez-Ruiz, Santiago (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). ISSN 1999-4923

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Official URL: https://doi.org/10.3390/pharmaceutics12060512




Abstract

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.


Item Type:Article
Additional Information:

Received: 29 April 2020 / Revised: 29 May 2020 / Accepted: 1 June 2020 / Published: 3 June 2020
(This article belongs to the Special Issue Metal-Based Drugs and Nanostructured Materials: New Trends in Bioactive Systems)

Uncontrolled Keywords:Tin; anticancer; mesoporous silica; folic acid; cytotoxicity; FOLR1
Subjects:Sciences > Chemistry > Materials
Medical sciences > Biology > Cytology
Medical sciences > Pharmacy > Organic chemistry
ID Code:61768
Deposited On:04 Aug 2020 10:09
Last Modified:29 Sep 2020 08:40

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