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CTX-CNF1 Recombinant Protein Selectively Targets Glioma Cells In Vivo

Current strategies for glioma treatment are only partly effective because of the poor selectivity for tumoral cells. Hence, the necessity to identify novel approaches is urgent. Recent studies highlighted the effectiveness of the bacterial protein cytotoxic necrotizing factor 1 (CNF1) in reducing tu...

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Autores principales: Vannini, Eleonora, Mori, Elisabetta, Tantillo, Elena, Schmidt, Gudula, Caleo, Matteo, Costa, Mario
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998600/
https://www.ncbi.nlm.nih.gov/pubmed/33800135
http://dx.doi.org/10.3390/toxins13030194
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author Vannini, Eleonora
Mori, Elisabetta
Tantillo, Elena
Schmidt, Gudula
Caleo, Matteo
Costa, Mario
author_facet Vannini, Eleonora
Mori, Elisabetta
Tantillo, Elena
Schmidt, Gudula
Caleo, Matteo
Costa, Mario
author_sort Vannini, Eleonora
collection PubMed
description Current strategies for glioma treatment are only partly effective because of the poor selectivity for tumoral cells. Hence, the necessity to identify novel approaches is urgent. Recent studies highlighted the effectiveness of the bacterial protein cytotoxic necrotizing factor 1 (CNF1) in reducing tumoral mass, increasing survival of glioma-bearing mice and protecting peritumoral neural tissue from dysfunction. However, native CNF1 needs to be delivered into the brain, because of its incapacity to cross the blood–brain barrier (BBB) per se, thus hampering its clinical translation. To allow a non-invasive administration of CNF1, we here developed a chimeric protein (CTX-CNF1) conjugating CNF1 with chlorotoxin (CTX), a peptide already employed in clinics due to its ability of passing the BBB and selectively binding glioma cells. After systemic administration, we found that CTX-CNF1 is able to target glioma cells and significantly prolong survival of glioma-bearing mice. Our data point out the potentiality of CTX-CNF1 as a novel effective tool to treat gliomas.
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spelling pubmed-79986002021-03-28 CTX-CNF1 Recombinant Protein Selectively Targets Glioma Cells In Vivo Vannini, Eleonora Mori, Elisabetta Tantillo, Elena Schmidt, Gudula Caleo, Matteo Costa, Mario Toxins (Basel) Communication Current strategies for glioma treatment are only partly effective because of the poor selectivity for tumoral cells. Hence, the necessity to identify novel approaches is urgent. Recent studies highlighted the effectiveness of the bacterial protein cytotoxic necrotizing factor 1 (CNF1) in reducing tumoral mass, increasing survival of glioma-bearing mice and protecting peritumoral neural tissue from dysfunction. However, native CNF1 needs to be delivered into the brain, because of its incapacity to cross the blood–brain barrier (BBB) per se, thus hampering its clinical translation. To allow a non-invasive administration of CNF1, we here developed a chimeric protein (CTX-CNF1) conjugating CNF1 with chlorotoxin (CTX), a peptide already employed in clinics due to its ability of passing the BBB and selectively binding glioma cells. After systemic administration, we found that CTX-CNF1 is able to target glioma cells and significantly prolong survival of glioma-bearing mice. Our data point out the potentiality of CTX-CNF1 as a novel effective tool to treat gliomas. MDPI 2021-03-08 /pmc/articles/PMC7998600/ /pubmed/33800135 http://dx.doi.org/10.3390/toxins13030194 Text en © 2021 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 (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Communication
Vannini, Eleonora
Mori, Elisabetta
Tantillo, Elena
Schmidt, Gudula
Caleo, Matteo
Costa, Mario
CTX-CNF1 Recombinant Protein Selectively Targets Glioma Cells In Vivo
title CTX-CNF1 Recombinant Protein Selectively Targets Glioma Cells In Vivo
title_full CTX-CNF1 Recombinant Protein Selectively Targets Glioma Cells In Vivo
title_fullStr CTX-CNF1 Recombinant Protein Selectively Targets Glioma Cells In Vivo
title_full_unstemmed CTX-CNF1 Recombinant Protein Selectively Targets Glioma Cells In Vivo
title_short CTX-CNF1 Recombinant Protein Selectively Targets Glioma Cells In Vivo
title_sort ctx-cnf1 recombinant protein selectively targets glioma cells in vivo
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998600/
https://www.ncbi.nlm.nih.gov/pubmed/33800135
http://dx.doi.org/10.3390/toxins13030194
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