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Open AccessArticle

Role of Folic Acid in the Therapeutic Action of Nanostructured Porous Silica Functionalized with Organotin(IV) Compounds against Different Cancer Cell Lines

1
COMET-NANO Group, Departamento de Biología y Geología, Física y Química Inorgánica, ESCET, Universidad Rey Juan Carlos, 28933 Móstoles, Spain
2
Tumour Biology Department, the Institute of Oncology “Prof. Dr. I. Chiricuta”, RO-400015 Cluj-Napoca, Romania
3
Innate Immunity Group, Laboratory of Tumour Immunology, IdiPAZ Institute for Health Research, La Paz University Hospital, 28046 Madrid, Spain
4
Department of Surgery, the Institute of Oncology “Prof. Dr. I. Chiricuta”, RO-400015 Cluj-Napoca, Romania
5
Department of Surgery and Gynecological Oncology, the University of Medicine and Pharmacy “Iuliu Hatieganu”, RO-400337 Cluj-Napoca, Romania
6
Departamento de Química Inorgánica, Universidad de Granada, Facultad de Ciencias, Campus de Fuentenueva, Avda. Fuentenueva s/n, E-18071 Granada, Spain
7
Nanobiotechnology for Life Sciences Group, Department of Chemistry in Pharmaceutical Sciences, Faculty of Pharmacy, Universidad Complutense de Madrid (UCM), Plaza Ramón y Cajal s/n, E-28040 Madrid, Spain
8
Microscopy and Dynamic Imaging Unit, Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Calle Melchor Fernandez Almagro 3, E-28029 Madrid, Spain
9
Medfuture-Research Center for Advanced Medicine, the University of Medicine and Pharmacy “Iuliu Hatieganu”, RO-400337 Cluj-Napoca, Romania
*
Authors to whom correspondence should be addressed.
Pharmaceutics 2020, 12(6), 512; https://doi.org/10.3390/pharmaceutics12060512
Received: 29 April 2020 / Revised: 29 May 2020 / Accepted: 1 June 2020 / Published: 3 June 2020
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. View Full-Text
Keywords: tin; anticancer; mesoporous silica; folic acid; cytotoxicity; FOLR1 tin; anticancer; mesoporous silica; folic acid; cytotoxicity; FOLR1
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Díaz-García, D.; Montalbán-Hernández, K.; Mena-Palomo, I.; Achimas-Cadariu, P.; Rodríguez-Diéguez, A.; López-Collazo, E.; Prashar, S.; Ovejero Paredes, K.; Filice, M.; Fischer-Fodor, E.; Gómez-Ruiz, S. Role of Folic Acid in the Therapeutic Action of Nanostructured Porous Silica Functionalized with Organotin(IV) Compounds against Different Cancer Cell Lines. Pharmaceutics 2020, 12, 512.

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