Journal
RSC ADVANCES
Volume 5, Issue 86, Pages 70352-70360Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c5ra14044g
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Funding
- National Research Council of Science and Technology (NST) through the Degree and Research Center (DRC) Program
- Basic Science Research Programs of MSIP [20100027955, 2015R1A2A2A05001390]
- LG Yonam Foundation
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In an attempt to develop biostable nanoparticles (NPs) as potential carriers of anticancer drugs, we prepared a triblock copolymer that can self-assemble into NPs and be gold cross-linked in aqueous conditions. The triblock copolymer, composed of poly(epsilon-caprolactone)-block-poly(2-(dimethylamino) ethyl methacrylate)-block-poly(ethylene glycol) (PCL-b-PDMAEMA-b-PEG), was synthesized by a combination of ring-opening polymerization, atom transfer radical polymerization and click chemistry. The chemical structures and compositions of the triblock copolymer and its intermediates were characterized by FT-IR and H-1 NMR. The triblock copolymer formed spherical NPs (195 nm in diameter) in PBS (pH 7.4). The anticancer drug, doxorubicin (DOX), was loaded into the NPs using a dialysis method. Tertiary amine groups, present in the PDMAEMA block of the triblock polymer, were used for in situ gold cross-linking, which was confirmed using transmission electron microscopy and UV/VIS spectroscopy. Bare NPs released 80% of DOX over 6 days, whereas only 40% of the DOX was released from gold cross-linked NPs (GNPs), implying that the gold cross-links act as a diffusion barrier of DOX. Owing to the slow release of DOX, the cytotoxicity of DOX-GNPs was much lower than that of DOX-loaded bare NPs. The blood concentrations of DOX were also monitored after intravenous injection of free DOX and DOX-loaded NPs into the tail veins of rats. The results indicated that the blood circulation time of DOX was longest for DOX-GNP, followed by DOX-NP, and free DOX. Overall, DOX-GNPs may be a promising carrier for hydrophobic anticancer drugs.
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