One of the major goals of precision oncology is to promote combination
therapy to improve efficacy and reduce side effects of anti-
cancer drugs based on their molecular mechanisms. In this study, we aimed to develop and validate new nanoformulations of
docetaxel (DTX) and
bortezomib (BTZ) for targeted combination
therapy to treat human
esophageal cancer. By leveraging our versatile
disulfide cross-linked
micelles (DCMs) platform, we developed nanoformulations of DTX and BTZ (named DTX-DCMs and BTZ-DCMs). Their physical properties were characterized; their anti-
cancer efficacies and mechanisms of action were investigated in a human
esophageal cancer cell line in vitro. Furthermore, the in vitro anti-
tumor activities of combination
therapies (concurrent drug treatment, sequential drug treatment, and treatment using different ratios of the drugs) were examined in comparison with the single drug treatment and free drug strategies. These drug-loaded nanoparticles were spherical in shape and relatively small in size of approximately 20-22 nm. The entrapment efficiencies of DTX and BTZ into nanoparticles were 82.4% and 84.1%, respectively. The drug release rates of DTX-DCMs and BTZ-DCMs were sustained, and greatly increased in the presence of GSH. These nanodrugs were effectively internalized by KYSE30
esophageal cancer cells, and dose-dependently induced cell apoptosis. We further revealed a strong synergistic effect between DTX-DCMs and BTZ-DCMs against KYSE30
esophageal cancer cells. Sequential combination
therapy with DTX-DCMs followed by BTZ-DCMs exhibited the best anti-
tumor efficacy in vitro. This study demonstrates that DTX and BTZ could be successfully nanoformulated into
disulfide cross-linked
micelles. The nanoformulations of DTX and BTZ demonstrate an immense potential for synergistic combination
therapy to treat human
esophageal cancer.