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

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...

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Autores: Ovejero Paredes, Karina, Díaz García, Diana, García Almodóvar, Victoria, Lozano Chamizo, Laura, Marciello, Marzia, Díaz-Sánchez, Miguel, Prashar, Sanjiv, Gómez-Ruiz, Santiago, Filice, Marco
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/8312
Acceso en línea:https://hdl.handle.net/20.500.14352/8312
Access Level:acceso abierto
Palabra clave:triple negative breast cancer
organotin
mesoporous silica nanoparticles
MDA-MB-231
theranostic nanomaterials
nanobiotechnology
molecular imaging
Farmacología (Farmacia)
Química farmaceútica
3209 Farmacología
2390 Química Farmacéutica
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network_name_str España
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spelling Multifunctional Silica-Based Nanoparticles with Controlled Release of Organotin Metallodrug for Targeted Theranosis of Breast CancerOvejero Paredes, KarinaDíaz García, DianaGarcía Almodóvar, VictoriaLozano Chamizo, LauraMarciello, MarziaDíaz-Sánchez, MiguelPrashar, SanjivGómez-Ruiz, SantiagoFilice, Marcotriple negative breast cancerorganotinmesoporous silica nanoparticlesMDA-MB-231theranostic nanomaterialsnanobiotechnologymolecular imagingFarmacología (Farmacia)Química farmaceútica3209 Farmacología2390 Química FarmacéuticaThree 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.MDPIUniversidad Complutense de Madrid20202020-01-1220202020-01-12journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/8312reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 3.0 Españahttps://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/83122026-06-02T12:44:21Z
dc.title.none.fl_str_mv Multifunctional Silica-Based Nanoparticles with Controlled Release of Organotin Metallodrug for Targeted Theranosis of Breast Cancer
title Multifunctional Silica-Based Nanoparticles with Controlled Release of Organotin Metallodrug for Targeted Theranosis of Breast Cancer
spellingShingle Multifunctional Silica-Based Nanoparticles with Controlled Release of Organotin Metallodrug for Targeted Theranosis of Breast Cancer
Ovejero Paredes, Karina
triple negative breast cancer
organotin
mesoporous silica nanoparticles
MDA-MB-231
theranostic nanomaterials
nanobiotechnology
molecular imaging
Farmacología (Farmacia)
Química farmaceútica
3209 Farmacología
2390 Química Farmacéutica
title_short Multifunctional Silica-Based Nanoparticles with Controlled Release of Organotin Metallodrug for Targeted Theranosis of Breast Cancer
title_full Multifunctional Silica-Based Nanoparticles with Controlled Release of Organotin Metallodrug for Targeted Theranosis of Breast Cancer
title_fullStr Multifunctional Silica-Based Nanoparticles with Controlled Release of Organotin Metallodrug for Targeted Theranosis of Breast Cancer
title_full_unstemmed Multifunctional Silica-Based Nanoparticles with Controlled Release of Organotin Metallodrug for Targeted Theranosis of Breast Cancer
title_sort Multifunctional Silica-Based Nanoparticles with Controlled Release of Organotin Metallodrug for Targeted Theranosis of Breast Cancer
dc.creator.none.fl_str_mv Ovejero Paredes, Karina
Díaz García, Diana
García Almodóvar, Victoria
Lozano Chamizo, Laura
Marciello, Marzia
Díaz-Sánchez, Miguel
Prashar, Sanjiv
Gómez-Ruiz, Santiago
Filice, Marco
author Ovejero Paredes, Karina
author_facet Ovejero Paredes, Karina
Díaz García, Diana
García Almodóvar, Victoria
Lozano Chamizo, Laura
Marciello, Marzia
Díaz-Sánchez, Miguel
Prashar, Sanjiv
Gómez-Ruiz, Santiago
Filice, Marco
author_role author
author2 Díaz García, Diana
García Almodóvar, Victoria
Lozano Chamizo, Laura
Marciello, Marzia
Díaz-Sánchez, Miguel
Prashar, Sanjiv
Gómez-Ruiz, Santiago
Filice, Marco
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv triple negative breast cancer
organotin
mesoporous silica nanoparticles
MDA-MB-231
theranostic nanomaterials
nanobiotechnology
molecular imaging
Farmacología (Farmacia)
Química farmaceútica
3209 Farmacología
2390 Química Farmacéutica
topic triple negative breast cancer
organotin
mesoporous silica nanoparticles
MDA-MB-231
theranostic nanomaterials
nanobiotechnology
molecular imaging
Farmacología (Farmacia)
Química farmaceútica
3209 Farmacología
2390 Química Farmacéutica
description 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.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020-01-12
2020
2020-01-12
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/8312
url https://hdl.handle.net/20.500.14352/8312
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 3.0 España
https://creativecommons.org/licenses/by/3.0/es/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 3.0 España
https://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.301629

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