Tumor vasculature-targeted (10)B delivery by an Annexin A1-binding peptide boosts effects of boron neutron capture therapy

BACKGROUND: p-Boronophenylalanine ((10)BPA) is a powerful (10)B drug used in current clinical trials of BNCT. For BNCT to be successful, a high (500 mg/kg) dose of (10)BPA must be administered over a few hours. Here, we report BNCT efficacy after rapid, ultralow-dose administration of either tumor vasculature-specific annexin A1-targeting IFLLWQR (IF7)-conjugated (10)BPA or borocaptate sodium ((10)BSH). METHODS: (1) IF7 conjugates of either (10)B drugs intravenously injected into MBT2 bladder tumor-bearing mice and biodistribution of (10)B in tumors and normal organs analyzed by prompt gamma-ray analysis. (2) Therapeutic effect of IF7-(10)B drug-mediated BNCT was assessed by either MBT2 bladder tumor bearing C3H/He mice and YTS-1 tumor bearing nude mice. RESULTS: Intravenous injection of IF7C conjugates of either (10)B drugs into MBT2 bladder tumor-bearing mice promoted rapid (10)B accumulation in tumor and suppressed tumor growth. Moreover, multiple treatments at ultralow (10–20 mg/kg) doses of IF7-(10)B drug-mediated BNCT significantly suppressed tumor growth in a mouse model of human YTS-1 bladder cancer, with increased Anxa1 expression in tumors and infiltration by CD8-positive lymphocytes. CONCLUSIONS: We conclude that IF7 serves as an efficient (10)B delivery vehicle by targeting tumor tissues via the tumor vasculature and could serve as a relevant vehicle for BNCT drugs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-020-07760-x.