Novel radiation-activated N-oxide prodrugs for highly selective and synergistic tumor therapy to promote DNA damage and the ATM/ATR pathway

Abstract

The novel radiation-activated prodrug NOS, derived from sorafenib, is reduced by hydrated electrons (e_aq⁻) to enable synergistic and highly selective chemo-radiotherapy. NOS exerts its inhibitory effect by inducing DNA damage and activating the ATM/ATR pathway, effectively achieving a 90.5% tumor inhibition rate in a liver cancer xenograft model.