1 research outputs found
Production of Cisplatin-Incorporating Hyaluronan Nanogels via Chelating Ligand–Metal Coordination
Hyaluronan
(HA) is a promising drug carrier for cancer therapy
because of its CD44 targeting ability, good biocompatibility, and
biodegradability. In this study, cisplatin (CDDP)-incorporating HA
nanogels were fabricated through a chelating ligand–metal coordination
cross-linking reaction. We conjugated chelating ligands, iminodiacetic
acid or malonic acid, to HA and used them as a precursor polymer.
By mixing the ligand-conjugated HA with CDDP, cross-linking occurred
via coordination of the ligands with the platinum in CDDP, resulting
in the spontaneous formation of CDDP-loaded HA nanogels. The nanogels
showed pH-responsive release of CDDP, because the stability of the
ligand–platinum complex decreases in an acidic environment.
Cell viability assays for MKN45P human gastric cancer cells and Met-5A
human mesothelial cells revealed that the HA nanogels selectively
inhibited the growth of gastric cancer cells. In vivo experiments
using a mouse model of peritoneal dissemination of gastric cancer
demonstrated that HA nanogels specifically localized in peritoneal
nodules after the intraperitoneal administration. Moreover, penetration
assays using multicellular tumor spheroids indicated that HA nanogels
had a significantly higher ability to penetrate tumors than conventional,
linear HA. These results suggest that chelating-ligand conjugated
HA nanogels will be useful for targeted cancer therapy