Cargando…
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...
Autores principales: | , , , , , , , , , |
---|---|
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 |
_version_ | 1785048919273635840 |
---|---|
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. |
format | Online Article Text |
id | pubmed-10219057 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT marchettiluca peptidefunctionalizedanddrugloadedtomatobushystuntvirusnanoparticlescounteracttumorgrowthinamousemodelofshhdependentmedulloblastoma AT novelliflavia peptidefunctionalizedanddrugloadedtomatobushystuntvirusnanoparticlescounteracttumorgrowthinamousemodelofshhdependentmedulloblastoma AT tannobarbara peptidefunctionalizedanddrugloadedtomatobushystuntvirusnanoparticlescounteracttumorgrowthinamousemodelofshhdependentmedulloblastoma AT leonardisimona peptidefunctionalizedanddrugloadedtomatobushystuntvirusnanoparticlescounteracttumorgrowthinamousemodelofshhdependentmedulloblastoma AT hizamveronicamohamed peptidefunctionalizedanddrugloadedtomatobushystuntvirusnanoparticlescounteracttumorgrowthinamousemodelofshhdependentmedulloblastoma AT arcangelicaterina peptidefunctionalizedanddrugloadedtomatobushystuntvirusnanoparticlescounteracttumorgrowthinamousemodelofshhdependentmedulloblastoma AT santiluca peptidefunctionalizedanddrugloadedtomatobushystuntvirusnanoparticlescounteracttumorgrowthinamousemodelofshhdependentmedulloblastoma AT baschieriselene peptidefunctionalizedanddrugloadedtomatobushystuntvirusnanoparticlescounteracttumorgrowthinamousemodelofshhdependentmedulloblastoma AT licochiara peptidefunctionalizedanddrugloadedtomatobushystuntvirusnanoparticlescounteracttumorgrowthinamousemodelofshhdependentmedulloblastoma AT mancusomariateresa peptidefunctionalizedanddrugloadedtomatobushystuntvirusnanoparticlescounteracttumorgrowthinamousemodelofshhdependentmedulloblastoma |