The feasibility of
boron neutron capture therapy (BNCT) greatly depends on the selective accumulation of 10B in
tumors. The
p-boronophenylalanine-fructose (
BPA-f) complex has been established as a conventional BNCT agent due to its preferential uptake into
tumors, which is driven by
amino acid transporters. However, the retention of
BPA-f in
tumors is highly limited because of an antiport mechanism, which is regulated by a gradient of
amino acid concentration across the
cancer cell membrane. Thus, to preserve a high 10B concentration in
tumors, patients are inevitably subjected to a constant
intravenous infusion. To this end, we employed a
phenylboronic acid (PBA)-decorated polymeric nanoparticle (NanoPBA) as a
sialic acid-targeting BNCT agent. In this manner, the PBA can exhibit dual functionalities, i.e., exhibiting a neutron capture capacity and hypersialyated
cancer cell targeting effect. Our developed NanoPBA possesses a supramolecular structure composed of a core and shell comprised of
poly(lactic acid) (PLA) and poly(
ethylene glycol) (PEG) segments, respectively. The PBA moiety is installed at the PEG end, providing an unusually strong targeting effect, supposedly via multivalent binding onto the
cancer cell membrane. As in BNCT, we verified the feasibility of NanoPBA against a
B16 melanoma-bearing mouse model. By virtue of efficient
tumor targeting, even at a 100-fold lower dose than
BPA-f, the NanoPBA achieved a potent antitumor effect.