Abstract
Amphiphilic oxidation-responsive prodrug (HPPCD) was firstly designed and synthesized in this study for resolving the hydrophobic nature of first-line anticancer drug paclitaxel (PTX), which was composed of hydrophilic β-cyclodextrin units and hyaluronic acid (HA) units. According to the biocompatibility and binding affinity between the synthetic conjugates and PTX, nanoparticles were prepared self-assembly. The solubilization were measured to be ca. 8000-fold increase compared to free paclitaxel (PTX), indicating about 2 mg/mL of solubility. In addition, cytotoxicity and wound healing assays showed the anticancer ability of the nanoparticles. The cellular investigations exhibited the time-dependent internalization and HA-mediated endocytosis. Apoptosis and cell cycle assays were performed to prove the retardation and further apoptosis. Three-dimensional spheroids (3DS) were constructed to mimic the tumors in vivo and further verify the anticancer capacity. Collectively these findings present HPPCD can be the potential insight as the carrier for hydrophobic drugs and further improve the cancer therapy.
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