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Grant support

This research was funded by Ministerio de Ciencia, Innovacion y Universidades of Spain (current Ministerio de Ciencia e Innovacion of Spain) grant numbers RTI2018-094322-B-I00 and CTQ2017-90802-REDT and Ministry of Research and Innovation, CNCS-UEFISCDI, project number PN-III-P4-ID-PCCF-2016-0142, within PNCDI III.

Analysis of institutional authors

Diaz-Garcia, DAuthorPrashar, SAuthorGomez-Ruiz, SCorresponding Author

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September 27, 2022
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Article

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

Publicated to:Pharmaceutics. 12 (6): 1-23 - 2020-06-01 12(6), DOI: 10.3390/pharmaceutics12060512

Authors: Diaz-Garcia, Diana; Montalban-Hernandez, Karla; Mena-Palomo, Irene; Achimas-Cadariu, Patriciu; Rodriguez-Dieguez, Antonio; Lopez-Collazo, Eduardo; Prashar, Sanjiv; Ovejero Paredes, Karina; Filice, Marco; Fischer-Fodor, Eva; Gomez-Ruiz, Santiago

Affiliations

Fdn Ctr Nacl Invest Cardiovasculares Carlos III C, Microscopy & Dynam Imaging Unit, Calle Melchor Fernandez Almagro 3, E-28029 Madrid, Spain - Author
Inst Oncol Prof Dr I Chiricuta, Dept Surg, RO-400015 Cluj Napoca, Romania - Author
Inst Oncol Prof Dr I Chiricuta, Tumour Biol Dept, RO-400015 Cluj Napoca, Romania - Author
La Paz Univ Hosp, IdiPAZ Inst Hlth Res, Lab Tumour Immunol, Innate Immun Grp, Madrid 28046, Spain - Author
Univ Complutense Madrid UCM, Fac Pharm, Dept Chem Pharmaceut Sci, Nanobiotechnol Life Sci Grp, Plaza Raman y Cajal S-N, E-28040 Madrid, Spain - Author
Univ Granada, Fac Ciencias, Dept Quim Inorgan, Campus Fuentenueva,Avda Fuentenueva S-N, E-18071 Granada, Spain - Author
Univ Med & Pharm Iuliu Hatieganu, Dept Surg & Gynecol Oncol, RO-400337 Cluj Napoca, Romania - Author
Univ Med & Pharm Iuliu Hatieganu, Medfuture Res Ctr Adv Med, RO-400337 Cluj Napoca, Romania - Author
Univ Rey Juan Carlos, Dept Biol & Geol Fis & Quim Inorgan, ESCET, COMET NANO Grp, Mostoles 28933, Spain - Author
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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-alpha and by the release of intracellular FR-alpha. 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.

Keywords

A-431 cell lineA2780 cell lineAbsorption spectroscopyAnticancerAntineoplastic activityArticleCancer cell lineControlled studyControlled-releaseCurcuminCytotoxicityDld-1 cell lineDrug delivery systemDrug targetingDrug-delivery systemEfficacyFemaleFolate receptorFolate receptor 1Folate-receptorFolic acidFolr1Glycosylphosphatidylinositol anchored proteinHumanHuman cellMesoporous silicaMesoporous silica nanoparticleMetal-complexesMicroscopyNanoparticlesOvcar-3 cell linePowderProtein expressionSba-15SynthesisTargeted deliveryTinTriphenyltinX ray diffractionX ray fluorescence

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Pharmaceutics due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2020, it was in position 29/276, thus managing to position itself as a Q1 (Primer Cuartil), in the category Pharmacology & Pharmacy. Notably, the journal is positioned above the 90th percentile.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 1.04. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 14, 2024)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

  • Weighted Average of Normalized Impact by the Scopus agency: 1.15 (source consulted: FECYT Feb 2024)
  • Field Citation Ratio (FCR) from Dimensions: 3.14 (source consulted: Dimensions Aug 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-08-07, the following number of citations:

  • WoS: 19
  • Scopus: 22
  • Europe PMC: 3

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-08-07:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 27.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 28 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 2.1.
  • The number of mentions on the social network X (formerly Twitter): 3 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Granada; Oman.

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Díaz García, Diana) and Last Author (Gómez Ruiz, Santiago).

the author responsible for correspondence tasks has been Gómez Ruiz, Santiago.