Journal
RSC ADVANCES
Volume 4, Issue 90, Pages 48943-48951Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c4ra08719d
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Funding
- National Natural Science Foundation of China [81272466]
- Provincial Youth Science Fund of Heilongjiang [QC2011C037]
- Heilongjiang Provincial Department of Education Fund for Scientific Research Technology Project [11511168]
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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 H-1 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 mu g 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.
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