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...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-03-01
|
| Series: | Toxins |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6651/13/3/194 |
| _version_ | 1797412420529946624 |
|---|---|
| author | Eleonora Vannini Elisabetta Mori Elena Tantillo Gudula Schmidt Matteo Caleo Mario Costa |
| author_facet | Eleonora Vannini Elisabetta Mori Elena Tantillo Gudula Schmidt Matteo Caleo Mario Costa |
| author_sort | Eleonora Vannini |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T05:02:43Z |
| format | Article |
| id | doaj.art-1f90cebb2cfe499da02dc261f6a52fd0 |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-03-09T05:02:43Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-1f90cebb2cfe499da02dc261f6a52fd02023-12-03T12:58:06ZengMDPI AGToxins2072-66512021-03-0113319410.3390/toxins13030194CTX-CNF1 Recombinant Protein Selectively Targets Glioma Cells In VivoEleonora Vannini0Elisabetta Mori1Elena Tantillo2Gudula Schmidt3Matteo Caleo4Mario Costa5Neuroscience Institute, National Research Council (CNR), via G. Moruzzi 1, 56124 Pisa, ItalyScuola Normale Superiore, 56126 Pisa, ItalyNeuroscience Institute, National Research Council (CNR), via G. Moruzzi 1, 56124 Pisa, ItalyMedizinische Fakultät, Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, University of Freiburg, 79085 Freiburg, GermanyNeuroscience Institute, National Research Council (CNR), via G. Moruzzi 1, 56124 Pisa, ItalyNeuroscience Institute, National Research Council (CNR), via G. Moruzzi 1, 56124 Pisa, ItalyCurrent 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.https://www.mdpi.com/2072-6651/13/3/194glioblastomadrug discoverycytotoxic necrotizing factor type 1chlorotoxinrecombinant protein productionglioma |
| spellingShingle | Eleonora Vannini Elisabetta Mori Elena Tantillo Gudula Schmidt Matteo Caleo Mario Costa CTX-CNF1 Recombinant Protein Selectively Targets Glioma Cells In Vivo Toxins glioblastoma drug discovery cytotoxic necrotizing factor type 1 chlorotoxin recombinant protein production glioma |
| 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 | glioblastoma drug discovery cytotoxic necrotizing factor type 1 chlorotoxin recombinant protein production glioma |
| url | https://www.mdpi.com/2072-6651/13/3/194 |
| work_keys_str_mv | AT eleonoravannini ctxcnf1recombinantproteinselectivelytargetsgliomacellsinvivo AT elisabettamori ctxcnf1recombinantproteinselectivelytargetsgliomacellsinvivo AT elenatantillo ctxcnf1recombinantproteinselectivelytargetsgliomacellsinvivo AT gudulaschmidt ctxcnf1recombinantproteinselectivelytargetsgliomacellsinvivo AT matteocaleo ctxcnf1recombinantproteinselectivelytargetsgliomacellsinvivo AT mariocosta ctxcnf1recombinantproteinselectivelytargetsgliomacellsinvivo |