The development of novel
therapeutics for patients with
bladder cancer is an important area of research, particularly considering the rather limited treatment options currently available. In this study, we designed and synthesized a conjugate of
cancer-targeting selenadiazole derivative BSeC (benzo[1,2,5]selenadiazole-5-
carboxylic acid) and the RGD (
arginine-
glycine-
aspartate)
peptide, which was used as a targeting molecule, using a PEI
polymer as a linker. The results showed that BSeC-PEI-RGD formed core-shell spherical nanoparticles with improved stability in physiological and low pH solutions. The
cancer-targeting design significantly enhanced cellular uptake of BSeC-PEI-RGD and decreased its cytotoxicity to normal cells. The nanoparticles could inhibit the migration and invasion of EJ and T24
bladder cancer cell and reduce
cancer cell proliferation through the induction of
reactive oxygen species (ROS)-dependent apoptosis and
mitochondrial dysfunction. Further mechanistic studies using western blotting showed that BSeC-PEI-RGD triggered
bladder cancer cell apoptosis by activating p38, JNK and p53 and by inactivating AKT and ERK. In summary, this study demonstrates the rational design of a
polymer-based
cancer-targeting nanosystem as a carrier of the selenadiazole derivative to treat
bladder cancer.