Fig. 6

Schematic showing proposed boost in therapeutic effect by IF7-¹⁰B drug mediated BNCT. a IF7-¹⁰B drugs are actively transported into tumor vascular endothelial or tumor cells by annexin A1 (Anxa1) expressed on the membrane of both cells types. Successful BNCT requires a ultralow dose (20 mg/kg) of IF7-¹⁰B drugs administered within 20 min. ¹⁰BPA is actively transported into tumor cells mainly by an L-type amino acid transporter 1 (LAT1) overexpressed in the membrane of many cancer cells. Successful BNCT requires a very high dose (500 mg/kg) of ¹⁰BPA administered over a few hours. ¹⁰BSH harbors 12 ¹⁰B atoms and is an efficient ¹⁰B carrier. ¹⁰BSH accumulates efficiently and shows enhanced permeability and retention (EPR) in tumors relative to normal tissue and is present only in intercellular spaces and not internalized by cells. b Therapeutic effects of current BNCT. ¹⁰B-containing cancer cells are effectively killed by neutron irradiation, but no cytotoxic effect is seen in the tumor vasculature. c Proposed therapeutic effect of active vascular and tumor targeting by IF7-¹⁰B drug-mediated BNCT. We propose that BNCT treatment upregulates Anxa1 in tumor tissues due to an inflammatory response or induced immunogenicity, and that more effective ¹⁰B accumulation in tumor tissues occurs following a second injection of IF7-¹⁰B drugs. IF7-¹⁰B drug-mediated BNCT likely destroys the Anxa1-positive tumor vasculature, boosting its therapeutic potential. Thus, multiple ultralow doses of IF7-¹⁰B drug-mediated BNCT may be required to maximize the therapeutic effect