Journal
TOXINS
Volume 13, Issue 3, Pages -Publisher
MDPI
DOI: 10.3390/toxins13030194
Keywords
glioblastoma; drug discovery; cytotoxic necrotizing factor type 1; chlorotoxin; recombinant protein production; glioma; brain tumor; drug delivery
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Funding
- AIRC [IG18925]
- PRIN project [20178L7WRS, SFB850]
- Fondazione Umberto Veronesi (Milan, Italy)
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The chimeric protein CTX-CNF1 shows potential as a novel effective tool for treating gliomas, targeting tumor cells and extending survival in mice by crossing the blood-brain barrier.
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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