o-FESAN Boron Molecule Sticks to DNA Despite Repulsion
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- ICMAB-CSIC researchers led by Clara Viñas found that o-FESAN — a negatively charged, iron-containing boron cluster — still intercalates into DNA because its outer hydrogen shell forms enough weak dihydrogen bonds to overcome the expected electrostatic repulsion, an effect the team likens to Velcro.
- o-FESAN slides into DNA between base pairs without provoking immediate toxicity, meaning it could be delivered to tumors intact and activated later by particle or gamma irradiation, according to the paper in the journal Aggregate.
- The molecule is active under three separate radiotherapy modalities — boron neutron capture therapy (BNCT), proton boron fusion therapy (PBFT), and Mössbauer irradiation — because it contains both boron-10 and boron-11 isotopes plus iron-57, Viñas said.
- Viñas' team is now working to combine BNCT, which targets the ~20% of natural boron that is boron-10, with PBFT, which targets the ~80% that is boron-11, in order to exploit the full boron payload delivered to a tumor.
- Activating iron-57 via the Mössbauer effect produces a very short-range damaging effect that achieves the same therapeutic outcome with far smaller doses of compound and radiation, drastically reducing side effects, per Viñas.
- o-FESAN crosses cell membranes without a carrier and accumulates in the cell nucleus, where dihydrogen and C–H···O/N hydrogen bonds hold it in place between DNA base pairs, the study reports.
Why it matters: If clinical work confirms o-FESAN's safety profile, cancer patients could receive a single injected agent that is later activated by whichever of three radiation sources a hospital has on hand — BNCT, PBFT, or Mössbauer gamma — turning today's boron-specific therapies into a flexible, lower-dose platform that uses both boron-10 and boron-11 instead of discarding 80% of the delivered payload.
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