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Peptide-Functionalized and Drug-Loaded Tomato Bushy Stunt Virus Nanoparticles Counteract Tumor Growth in a Mouse Model of Shh-Dependent Medulloblastoma

Sonic hedgehog medulloblastoma (SHH-MB) accounts for 25–30% of all MBs, and conventional therapy results in severe long-term side effects. New targeted therapeutic approaches are urgently needed, drawing also on the fields of nanoparticles (NPs). Among these, plant viruses are very promising, and we...

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Autores principales: Marchetti, Luca, Novelli, Flavia, Tanno, Barbara, Leonardi, Simona, Hizam, Veronica Mohamed, Arcangeli, Caterina, Santi, Luca, Baschieri, Selene, Lico, Chiara, Mancuso, Mariateresa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10219057/
https://www.ncbi.nlm.nih.gov/pubmed/37240259
http://dx.doi.org/10.3390/ijms24108911
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author Marchetti, Luca
Novelli, Flavia
Tanno, Barbara
Leonardi, Simona
Hizam, Veronica Mohamed
Arcangeli, Caterina
Santi, Luca
Baschieri, Selene
Lico, Chiara
Mancuso, Mariateresa
author_facet Marchetti, Luca
Novelli, Flavia
Tanno, Barbara
Leonardi, Simona
Hizam, Veronica Mohamed
Arcangeli, Caterina
Santi, Luca
Baschieri, Selene
Lico, Chiara
Mancuso, Mariateresa
author_sort Marchetti, Luca
collection PubMed
description Sonic hedgehog medulloblastoma (SHH-MB) accounts for 25–30% of all MBs, and conventional therapy results in severe long-term side effects. New targeted therapeutic approaches are urgently needed, drawing also on the fields of nanoparticles (NPs). Among these, plant viruses are very promising, and we previously demonstrated that tomato bushy stunt virus (TBSV), functionalized on the surface with CooP peptide, specifically targets MB cells. Here, we tested the hypothesis that TBSV-CooP can specifically deliver a conventional chemotherapeutic drug (i.e., doxorubicin, DOX) to MB in vivo. To this aim, a preclinical study was designed to verify, by histological and molecular methods, if multiple doses of DOX-TBSV-CooP were able to inhibit tumor progression of MB pre-neoplastic lesions, and if a single dose was able to modulate pro-apoptotic/anti-proliferative molecular signaling in full-blown MBs. Our results demonstrate that when DOX is encapsulated in TBSV-CooP, its effects on cell proliferation and cell death are similar to those obtained with a five-fold higher dose of non-encapsulated DOX, both in early and late MB stages. In conclusion, these results confirm that CooP-functionalized TBSV NPs are efficient carriers for the targeted delivery of therapeutics to brain tumors.
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spelling pubmed-102190572023-05-27 Peptide-Functionalized and Drug-Loaded Tomato Bushy Stunt Virus Nanoparticles Counteract Tumor Growth in a Mouse Model of Shh-Dependent Medulloblastoma Marchetti, Luca Novelli, Flavia Tanno, Barbara Leonardi, Simona Hizam, Veronica Mohamed Arcangeli, Caterina Santi, Luca Baschieri, Selene Lico, Chiara Mancuso, Mariateresa Int J Mol Sci Article Sonic hedgehog medulloblastoma (SHH-MB) accounts for 25–30% of all MBs, and conventional therapy results in severe long-term side effects. New targeted therapeutic approaches are urgently needed, drawing also on the fields of nanoparticles (NPs). Among these, plant viruses are very promising, and we previously demonstrated that tomato bushy stunt virus (TBSV), functionalized on the surface with CooP peptide, specifically targets MB cells. Here, we tested the hypothesis that TBSV-CooP can specifically deliver a conventional chemotherapeutic drug (i.e., doxorubicin, DOX) to MB in vivo. To this aim, a preclinical study was designed to verify, by histological and molecular methods, if multiple doses of DOX-TBSV-CooP were able to inhibit tumor progression of MB pre-neoplastic lesions, and if a single dose was able to modulate pro-apoptotic/anti-proliferative molecular signaling in full-blown MBs. Our results demonstrate that when DOX is encapsulated in TBSV-CooP, its effects on cell proliferation and cell death are similar to those obtained with a five-fold higher dose of non-encapsulated DOX, both in early and late MB stages. In conclusion, these results confirm that CooP-functionalized TBSV NPs are efficient carriers for the targeted delivery of therapeutics to brain tumors. MDPI 2023-05-17 /pmc/articles/PMC10219057/ /pubmed/37240259 http://dx.doi.org/10.3390/ijms24108911 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Marchetti, Luca
Novelli, Flavia
Tanno, Barbara
Leonardi, Simona
Hizam, Veronica Mohamed
Arcangeli, Caterina
Santi, Luca
Baschieri, Selene
Lico, Chiara
Mancuso, Mariateresa
Peptide-Functionalized and Drug-Loaded Tomato Bushy Stunt Virus Nanoparticles Counteract Tumor Growth in a Mouse Model of Shh-Dependent Medulloblastoma
title Peptide-Functionalized and Drug-Loaded Tomato Bushy Stunt Virus Nanoparticles Counteract Tumor Growth in a Mouse Model of Shh-Dependent Medulloblastoma
title_full Peptide-Functionalized and Drug-Loaded Tomato Bushy Stunt Virus Nanoparticles Counteract Tumor Growth in a Mouse Model of Shh-Dependent Medulloblastoma
title_fullStr Peptide-Functionalized and Drug-Loaded Tomato Bushy Stunt Virus Nanoparticles Counteract Tumor Growth in a Mouse Model of Shh-Dependent Medulloblastoma
title_full_unstemmed Peptide-Functionalized and Drug-Loaded Tomato Bushy Stunt Virus Nanoparticles Counteract Tumor Growth in a Mouse Model of Shh-Dependent Medulloblastoma
title_short Peptide-Functionalized and Drug-Loaded Tomato Bushy Stunt Virus Nanoparticles Counteract Tumor Growth in a Mouse Model of Shh-Dependent Medulloblastoma
title_sort peptide-functionalized and drug-loaded tomato bushy stunt virus nanoparticles counteract tumor growth in a mouse model of shh-dependent medulloblastoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10219057/
https://www.ncbi.nlm.nih.gov/pubmed/37240259
http://dx.doi.org/10.3390/ijms24108911
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