1 research outputs found
Structural Determination of the Nanocomplex of Borate with Styrene–Maleic Acid Copolymer-Conjugated Glucosamine Used as a Multifunctional Anticancer Drug
The
development of effective anticancer drugs is essential for
chemotherapy that specifically targets cancer tissues. We recently
synthesized a multifunctional water-soluble anticancer polymer drug
consisting of styrene–maleic acid copolymer (SMA) conjugated
with glucosamine and boric acid (BA) (SGB complex). It demonstrated
about 10 times higher tumor-selective accumulation compared with accumulation
in normal tissues because of the enhanced permeability and retention
effect, and it inhibited tumor growth via glycolysis inhibition, mitochondrial
damage, and thermal neutron irradiation. Gaining insight into the
anticancer effects of this SGB complex requires a determination of
its structure. We therefore investigated the chemical structure of
the SGB complex by means of nuclear magnetic resonance, infrared (IR)
spectroscopy, and liquid chromatography–mass spectrometry.
To establish the chemical structure of the SGB complex, we synthesized
a simple model compoundmaleic acid–glucosamine (MAG)
conjugateby using a maleic anhydride (MA) monomer unit instead
of the SMA polymer. We obtained two MAG–BA complexes (MAGB)
with molecular weights of 325 and 343 after the MAG reaction with
BA. We confirmed, by using IR spectroscopy, that MAGB formed a stable
complex via an amide bond between MA and glucosamine and that BA bound
to glucosamine via a diol bond. As a result of this chemical design,
identified via analysis of MAGB, the SGB complex can release BA and
demonstrate toxicity to cancer cells through inhibition of lactate
secretion in mild hypoxia that mimics the tumor microenvironment.
For clinical application of the SGB complex, we confirmed that this
complex is stable in the presence of serum. These findings confirm
that our design of the SGB complex has various advantages in targeting
solid cancers and exerting therapeutic effects when combined with
neutron irradiation