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 Ph<sub>3</sub>Sn{SCH<sub>2</sub>CH<sub>2</sub>CH<sub>2</sub>Si(OMe)<su...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-01-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/1/187 |
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| author | Karina Ovejero Paredes Diana Díaz-García Victoria García-Almodóvar Laura Lozano Chamizo Marzia Marciello Miguel Díaz-Sánchez Sanjiv Prashar Santiago Gómez-Ruiz Marco Filice |
| author_facet | Karina Ovejero Paredes Diana Díaz-García Victoria García-Almodóvar Laura Lozano Chamizo Marzia Marciello Miguel Díaz-Sánchez Sanjiv Prashar Santiago Gómez-Ruiz Marco Filice |
| author_sort | Karina Ovejero Paredes |
| collection | DOAJ |
| description | Three different multifunctional nanosystems based on the tethering onto mesoporous silica nanoparticles (MSN) of different fragments such as an organotin-based cytotoxic compound Ph<sub>3</sub>Sn{SCH<sub>2</sub>CH<sub>2</sub>CH<sub>2</sub>Si(OMe)<sub>3</sub>} (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. |
| first_indexed | 2024-03-12T07:24:17Z |
| format | Article |
| id | doaj.art-884e2f7f8aa645b5af0a9365b38a6e6b |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T07:24:17Z |
| publishDate | 2020-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-884e2f7f8aa645b5af0a9365b38a6e6b2023-09-02T22:11:34ZengMDPI AGCancers2072-66942020-01-0112118710.3390/cancers12010187cancers12010187Multifunctional Silica-Based Nanoparticles with Controlled Release of Organotin Metallodrug for Targeted Theranosis of Breast CancerKarina Ovejero Paredes0Diana Díaz-García1Victoria García-Almodóvar2Laura Lozano Chamizo3Marzia Marciello4Miguel Díaz-Sánchez5Sanjiv Prashar6Santiago Gómez-Ruiz7Marco Filice8Nanobiotechnology 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, SpainCOMET-NANO Group. Department of Biology and Geology, Physics and Inorganic Chemistry, ESCET, Universidad Rey Juan Carlos, Calle Tulipán s/n, E-28933 Móstoles (Madrid), SpainNanobiotechnology 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, SpainNanobiotechnology 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, SpainNanobiotechnology 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, SpainCOMET-NANO Group. Department of Biology and Geology, Physics and Inorganic Chemistry, ESCET, Universidad Rey Juan Carlos, Calle Tulipán s/n, E-28933 Móstoles (Madrid), SpainCOMET-NANO Group. Department of Biology and Geology, Physics and Inorganic Chemistry, ESCET, Universidad Rey Juan Carlos, Calle Tulipán s/n, E-28933 Móstoles (Madrid), SpainCOMET-NANO Group. Department of Biology and Geology, Physics and Inorganic Chemistry, ESCET, Universidad Rey Juan Carlos, Calle Tulipán s/n, E-28933 Móstoles (Madrid), SpainNanobiotechnology 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, SpainThree different multifunctional nanosystems based on the tethering onto mesoporous silica nanoparticles (MSN) of different fragments such as an organotin-based cytotoxic compound Ph<sub>3</sub>Sn{SCH<sub>2</sub>CH<sub>2</sub>CH<sub>2</sub>Si(OMe)<sub>3</sub>} (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.https://www.mdpi.com/2072-6694/12/1/187triple negative breast cancerorganotinmesoporous silica nanoparticlesmda-mb-231theranostic nanomaterialsnanobiotechnologymolecular imaging |
| spellingShingle | Karina Ovejero Paredes Diana Díaz-García Victoria García-Almodóvar Laura Lozano Chamizo Marzia Marciello Miguel Díaz-Sánchez Sanjiv Prashar Santiago Gómez-Ruiz Marco Filice Multifunctional Silica-Based Nanoparticles with Controlled Release of Organotin Metallodrug for Targeted Theranosis of Breast Cancer Cancers triple negative breast cancer organotin mesoporous silica nanoparticles mda-mb-231 theranostic nanomaterials nanobiotechnology molecular imaging |
| title | 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_short | 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 |
| topic | triple negative breast cancer organotin mesoporous silica nanoparticles mda-mb-231 theranostic nanomaterials nanobiotechnology molecular imaging |
| url | https://www.mdpi.com/2072-6694/12/1/187 |
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