Construction and evaluation of hyaluronic acid-based copolymers as a targeted chemotherapy drug carrier for cancer therapy

Melanoma (MM) is a highly aggressive skin cancer with limited treatment options. Although chemotherapy has been using for advanced melanoma treatment, the lack of targetability, the poor biocompatibility and the severe side effects still hamper the wide applications of chemotherapy agents in MM management. Herein, a biocompatible and biodegradable polymeric hyaluronic acid nanoparticle (HANP) encapsulated with Paclitaxel (PTX) was developed for MM targeted therapy. Our results showed that PTX at 37 +/- 2.1% (w/w) was able to be loaded into HANP with over five days of stability under physiological conditions. In vitro, HANP/PTX presented hyaluronidase-dependent drug release. Compared to free PTX, HANP/PTX demonstrated a 6-75 times higher growth inhibition in five different cancer cells, while only presenting minimum toxicity to normal cells. After intravenous administration at a 10 mg/kg equivalent dose of PTX, HANP/PTX significantly ablated MM tumor growth in a mouse model. As confirmed by 18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) imaging, the tumors started to respond to the HANP/PTX as early as seven days after the initial treatment, which will significantly benefit for personalized treatment. In conclusion, the HANP/PTX nanocomplex demonstrated great promise as a translational nanomedicine for cancer chemotherapy.