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Impact on the Sustainable Development Goals (SDGs)

Analysis of institutional authors

Diaz-Garcia, DAuthorGarcia-Almodovar, VAuthorDiaz-Sanchez, MAuthorPrashar, SAuthorGomez-Ruiz, SCorresponding Author

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September 27, 2022
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Article

Multifunctional Silica-Based Nanoparticles with Controlled Release of Organotin Metallodrug for Targeted Theranosis of Breast Cancer

Publicated to: Cancers. 12 (1): 187- - 2020-01-01 12(1), DOI: 10.3390/cancers12010187

Authors:

Paredes, KO; Díaz-García, D; García-Almodóvar, V; Chamizo, LL; Marciello, M; Díaz-Sánchez, M; Prashar, S; Gómez-Ruiz, S; Filice, M
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Affiliations

Fdn Ctr Nacl Invest Cardiovasc Carlos III CNIC, Microscopy & Dynam Imaging Unit, Calle Melchor Fernandez Almagro 3, E-28029 Madrid, Spain - Author
Univ Complutense Madrid, Fac Pharm, Dept Chem Pharmaceut Sci, Nanobiotechnol Life Sci Grp, Plaza Ramon y Cajal S-N, E-28040 Madrid, Spain - Author
Univ Rey Juan Carlos, ESCET, Dept Biol & Geol Phys & Inorgan Chem, COMET NANO Group, Calle Tulipan S-N, E-28933 Mostoles, Madrid, Spain - Author
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Abstract

Three different multifunctional nanosystems based on the tethering onto mesoporous silica nanoparticles (MSN) of different fragments such as an organotin-based cytotoxic compound Ph3Sn{SCH2CH2CH2Si(OMe)(3)} (MSN-AP-Sn), a folate fragment (MSN-AP-FA-Sn), and an enzyme-responsive peptide able to release the metallodrug only inside cancer cells (MSN-AP-FA-PEP-S-Sn), have been synthesized and fully characterized by applying physico-chemical techniques. After that, an in vitro deep determination of the therapeutic potential of the achieved multifunctional nanovectors was carried out. The results showed a high cytotoxic potential of the MSN-AP-FA-PEP-S-Sn material against triple negative breast cancer cell line (MDA-MB-231). Moreover, a dose-dependent metallodrug-related inhibitory effect on the migration mechanism of MDA-MB-231 tumor cells was shown. Subsequently, the organotin-functionalized nanosystems have been further modified with the NIR imaging agent Alexa Fluor 647 to give three different theranostic silica-based nanoplatforms, namely, MSN-AP-Sn-AX (AX-1), MSN-AP-FA-Sn-AX (AX-2), and MSN-AP-FA-PEP-S-Sn-AX (AX-3). Their in vivo potential as theranostic markers was further evaluated in a xenograft mouse model of human breast adenocarcinoma. Owing to the combination of the receptor-mediated site targeting and the specific fine-tuned release mechanism of the organotin metallodrug, the nanotheranostic drug MSN-AP-FA-PEP-S-Sn-AX (AX-3) has shown targeted diagnostic ability in combination with enhanced therapeutic activity by promoting the inhibition of tumor growth with reduced hepatic and renal toxicity upon the repeated administration of the multifunctional nanodrug.
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Keywords

3 ( aminopropyl)triethoxysilane3 mercaptopropyltrimethoxysilaneAnimal cellAnimal experimentAnimal modelAntineoplastic activityAntineoplastic agentArticleAx 1Ax 2Ax 3Breast adenocarcinomaCancer inhibitionCarboxylate complexesCathepsin-bCell cultureCell migrationCell transportCell viability assayCell-migrationControlled studyCytotoxicityDrug releaseDrug structureDrug-deliveryExpressionFemaleFolate receptorFolic acidGood health and well-beingHumanHuman cellIn vitro studyIn vivo studyLiver toxicityLong-termMda-mb-231Mda-mb-231 cell lineMesoporous silicaMesoporous silica nanoparticleMesoporous silica nanoparticlesMetal-complexesMolecular imagingMouseNanobiotechnologyNephrotoxicityNonhumanOrganotinOrganotin compoundTheranostic nanomaterialsTheranostic nanomedicineTherapyTriple negative breast cancerUnclassified drugWound healing assay

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Cancers 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 51/242, thus managing to position itself as a Q1 (Primer Cuartil), in the category Oncology.

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: 2.6. 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 13, 2025)

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: 2.36 (source consulted: FECYT Mar 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2026-04-02, the following number of citations:

  • WoS: 59
  • Scopus: 60
  • Europe PMC: 14
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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 2026-04-02:

  • 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: 53.
  • 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: 52 (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: 6.
  • The number of mentions on the social network X (formerly Twitter): 8 (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.
  • Assignment of a Handle/URN as an identifier within the deposit in the Institutional Repository: http://hdl.handle.net/20.500.14352/8312
Continuing with the social impact of the work, it is important to emphasize that, due to its content, it can be assigned to the area of interest of ODS 3 - Ensure healthy lives and promote well-being for all at all ages, with a probability of 73% according to the mBERT algorithm developed by Aurora University.
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Leadership analysis of institutional authors

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

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Project objectives

Los objetivos perseguidos en esta aportación se centran en el desarrollo y evaluación de nanosistemas multifuncionales para el tratamiento y diagnóstico dirigido del cáncer de mama. Se pretende sintetizar y caracterizar físicochemicalmente nanopartículas de sílice mesoporosa funcionalizadas con compuestos organoestánnicos citotóxicos, fragmentos de folato y péptidos sensibles a enzimas. Asimismo, se busca determinar in vitro el potencial terapéutico de estos nanovectores, evaluando su citotoxicidad y efecto inhibidor sobre la migración celular en líneas tumorales de cáncer de mama triple negativo. Además, se pretende modificar estos nanosistemas con agentes de imagen NIR para crear nanoplataformas teranósticas y evaluar su eficacia in vivo en modelos murinos xenoinjertados, analizando la capacidad diagnóstica dirigida y la actividad terapéutica con toxicidad reducida.
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Most relevant results

Se han desarrollado y caracterizado tres nanosistemas multifuncionales basados en nanopartículas de sílice mesoporosa con diferentes fragmentos para la liberación controlada de un compuesto organoestannoso. Los resultados principales son: (1) el nanosistema MSN-AP-FA-PEP-S-Sn mostró un alto potencial citotóxico frente a la línea celular de cáncer de mama triple negativo MDA-MB-231; (2) se evidenció un efecto inhibidor dependiente de la dosis sobre la migración celular tumoral; (3) la funcionalización con el agente de imagen NIR Alexa Fluor 647 permitió la obtención de tres nanoplataformas termanósticas; (4) en un modelo murino xenoinjertado, el nanosistema MSN-AP-FA-PEP-S-Sn-AX (AX-3) demostró capacidad diagnóstica dirigida y una actividad terapéutica mejorada con inhibición del crecimiento tumoral y reducción de toxicidad hepática y renal tras administración repetida.
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Awards linked to the item

The CNIC is supported by MINECO and the Pro-CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505). M.F. would like to thank MINECO for the research grant no. SAF2014-59118-JIN co-funded by Fondo Europeo de Desarrollo Regional (FEDER) and COST Action CA1520: European Network on NMR Relaxometry-EURELAX. M.F. acknowledges the Comunidad Autonoma de Madrid for research project no. 2017-T1/BIO-4992 (Atraccion de Talento Action) also cofunded by Universidad Complutense de Madrid. M.F. and K.O.P. are grateful to ICTS-ReDIB. M.M and M.F. are grateful to the Comunidad Autonoma de Madrid and FEDER for the I+D collaborative Programme in Biomedicine NIETO-CM (Project reference B2017-BMD3731). We would also like to thank the Ministerio de Ciencia, Innovacion y Universidades of Spain (grants numbers RTI2018-094322-B-I00 and CTQ2017-90802-REDT) for the funding and Direccion General de Investigacion e Innovacion, Consejeria de Educacion e Investigacion de la Comunidad de Madrid for the predoctoral grant PEJD-2017-PRE/AMB-4047 (M.D.-S.).
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