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Glioblastoma Multiforme Selective Nanomedicines for Improved Anti-Cancer Treatments

Glioblastoma Multiforme (GBM) is a devastating disease with a low survival rate and few efficacious treatment options. The fast growth, late diagnostics, and off-target toxicity of currently used drugs represent major barriers that need to be overcome to provide a viable cure. Nanomedicines (NMeds)...

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Autores principales: Duskey, Jason Thomas, Rinaldi, Arianna, Ottonelli, Ilaria, Caraffi, Riccardo, De Benedictis, Chiara Alessia, Sauer, Ann Katrin, Tosi, Giovanni, Vandelli, Maria Angela, Ruozi, Barbara, Grabrucker, Andreas Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9325049/
https://www.ncbi.nlm.nih.gov/pubmed/35890345
http://dx.doi.org/10.3390/pharmaceutics14071450
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author Duskey, Jason Thomas
Rinaldi, Arianna
Ottonelli, Ilaria
Caraffi, Riccardo
De Benedictis, Chiara Alessia
Sauer, Ann Katrin
Tosi, Giovanni
Vandelli, Maria Angela
Ruozi, Barbara
Grabrucker, Andreas Martin
author_facet Duskey, Jason Thomas
Rinaldi, Arianna
Ottonelli, Ilaria
Caraffi, Riccardo
De Benedictis, Chiara Alessia
Sauer, Ann Katrin
Tosi, Giovanni
Vandelli, Maria Angela
Ruozi, Barbara
Grabrucker, Andreas Martin
author_sort Duskey, Jason Thomas
collection PubMed
description Glioblastoma Multiforme (GBM) is a devastating disease with a low survival rate and few efficacious treatment options. The fast growth, late diagnostics, and off-target toxicity of currently used drugs represent major barriers that need to be overcome to provide a viable cure. Nanomedicines (NMeds) offer a way to overcome these pitfalls by protecting and loading drugs, increasing blood half-life, and being targetable with specific ligands on their surface. In this study, the FDA-approved polymer poly (lactic-co-glycolic) acid was used to optimise NMeds that were surface modified with a series of potential GBM-specific ligands. The NMeds were fully characterised for their physical and chemical properties, and then in vitro testing was performed to evaluate cell uptake and GBM cell specificity. While all targeted NMeds showed improved uptake, only those decorated with the-cell surface vimentin antibody M08 showed specificity for GBM over healthy cells. Finally, the most promising targeted NMed candidate was loaded with the well-known chemotherapeutic, paclitaxel, to confirm targeting and therapeutic effects in C6 GBM cells. These results demonstrate the importance of using well-optimised NMeds targeted with novel ligands to advance delivery and pharmaceutical effects against diseased cells while minimising the risk for nearby healthy cells.
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spelling pubmed-93250492022-07-27 Glioblastoma Multiforme Selective Nanomedicines for Improved Anti-Cancer Treatments Duskey, Jason Thomas Rinaldi, Arianna Ottonelli, Ilaria Caraffi, Riccardo De Benedictis, Chiara Alessia Sauer, Ann Katrin Tosi, Giovanni Vandelli, Maria Angela Ruozi, Barbara Grabrucker, Andreas Martin Pharmaceutics Article Glioblastoma Multiforme (GBM) is a devastating disease with a low survival rate and few efficacious treatment options. The fast growth, late diagnostics, and off-target toxicity of currently used drugs represent major barriers that need to be overcome to provide a viable cure. Nanomedicines (NMeds) offer a way to overcome these pitfalls by protecting and loading drugs, increasing blood half-life, and being targetable with specific ligands on their surface. In this study, the FDA-approved polymer poly (lactic-co-glycolic) acid was used to optimise NMeds that were surface modified with a series of potential GBM-specific ligands. The NMeds were fully characterised for their physical and chemical properties, and then in vitro testing was performed to evaluate cell uptake and GBM cell specificity. While all targeted NMeds showed improved uptake, only those decorated with the-cell surface vimentin antibody M08 showed specificity for GBM over healthy cells. Finally, the most promising targeted NMed candidate was loaded with the well-known chemotherapeutic, paclitaxel, to confirm targeting and therapeutic effects in C6 GBM cells. These results demonstrate the importance of using well-optimised NMeds targeted with novel ligands to advance delivery and pharmaceutical effects against diseased cells while minimising the risk for nearby healthy cells. MDPI 2022-07-12 /pmc/articles/PMC9325049/ /pubmed/35890345 http://dx.doi.org/10.3390/pharmaceutics14071450 Text en © 2022 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
Duskey, Jason Thomas
Rinaldi, Arianna
Ottonelli, Ilaria
Caraffi, Riccardo
De Benedictis, Chiara Alessia
Sauer, Ann Katrin
Tosi, Giovanni
Vandelli, Maria Angela
Ruozi, Barbara
Grabrucker, Andreas Martin
Glioblastoma Multiforme Selective Nanomedicines for Improved Anti-Cancer Treatments
title Glioblastoma Multiforme Selective Nanomedicines for Improved Anti-Cancer Treatments
title_full Glioblastoma Multiforme Selective Nanomedicines for Improved Anti-Cancer Treatments
title_fullStr Glioblastoma Multiforme Selective Nanomedicines for Improved Anti-Cancer Treatments
title_full_unstemmed Glioblastoma Multiforme Selective Nanomedicines for Improved Anti-Cancer Treatments
title_short Glioblastoma Multiforme Selective Nanomedicines for Improved Anti-Cancer Treatments
title_sort glioblastoma multiforme selective nanomedicines for improved anti-cancer treatments
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9325049/
https://www.ncbi.nlm.nih.gov/pubmed/35890345
http://dx.doi.org/10.3390/pharmaceutics14071450
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