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A convenient and efficient strategy was developed for accessing chlorotoxin-derived bicyclic peptide-biomolecule conjugates by cyclizing fully-unprotected linear peptides with a designed tetrafunctional chemical linker. Among these peptides, bicycle-P3 bearing the N-terminal sequence of chlorotoxin shows high tumor selectivity and penetration ability, which is promising for treatment of gliomas.

Graphical abstract: Chlorotoxin-derived bicyclic peptides for targeted imaging of glioblastomas

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