pH-responsive flower-like micelles constructed via oxime linkage for anticancer drug delivery

Abstract

A new type of pH-responsive flower-like micelle based on backbone-cleavable triblock copolymer polycaprolactone-oxime-poly(ethylene glycol)-oxime-polycaprolactone (PCL-OPEG-PCL) was developed for anticancer drug delivery. Firstly, PCL-OPEG-PCL was synthesized by ring-opening polymerization. The structure of PCL-OPEG-PCL was confirmed by ¹H NMR and Fourier transform infrared spectroscopy (FTIR). Benefiting from the amphiphilic character and unique molecular architecture with the hydrophilic PEG and hydrophobic PCL segments, PCL-OPEG-PCL could self-assemble into flower-like micelles in aqueous solution, which has been demonstrated by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The cytotoxicity of the flower-like micelles was evaluated by MTT assay against NIH/3T3 normal cells. Doxorubicin (DOX), a model anticancer drug, was encapsulated into these flower-like micelles with high efficiency. The in vitro study showed that DOX-loaded flower-like micelles possessed high stability at physiological pH of 7.4, whereas the DOX release from the flower-like micelles was significantly accelerated at mildly acidic pH of 5.0, demonstrating the pH-responsive feature of the drug carrier with oxime linkages. DOX-loaded flower-like micelles were investigated for proliferation inhibition of Hela cells in vitro, and the DOX dose required for 50% cellular growth inhibition was found to be 1.81 μg mL⁻¹. All of these results demonstrate that flower-like micelles self-assembled from PCL-OPEG-PCL triblock copolymers can be used as effective and promising drug nanocarriers.