Doxorubicin delivered by redox-responsive Hyaluronic Acid-Ibuprofen prodrug micelles for treatment of metastatic breast cancer

During the process of cancer metastasis, various enzymes, cytokines, and factors were involved, and upregulated cyclooxygenase-2(COX-2) in tumor cells led to proliferation and invasion of various tumors. Many nonsteroidal anti-inflammatory drugs (NSAIDs) were used as an anticancer adjuvant in chemotherapy, such as ibuprofen (BF) and celecoxib. NSAIDs could effectively inhibit local inflammation and decreased COX-2 expression. However, most of them have serious toxicity issues due to their limit selectivity against cancer and poor water solubility. Thus hyaluronic acid-ibuprofen (HA-ss-BF), which was sensitive to the reducing environment, was prepared by binding ibuprofen (BF) to the hyaluronic acid backbone through a disulfide bond, and the HA-ss-BF polymer could self-assemble into micelles and serve as carriers to delivery doxorubicin. These redox-sensitive prodrug polymeric micelles hold multiple therapeutic advantages, including on-demand BF release and disassembling micelles responding to redox stimuli, as well as desirable cellular uptake and favorable biodistribution. These advantages indicated the redox-responsive hyaluronic acid-ibuprofen prodrug could be a promising delivery system for metastatic breast cancer treatment.