Journal
JOURNAL OF MATERIALS CHEMISTRY
Volume 22, Issue 15, Pages 7121-7129Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c2jm15277k
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Funding
- NSERC
- NSERC RTI
- Manitoba Children's Foundation
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This study developed novel reducible micelles that are approximately 100 nm in diameter and consist of poly(beta-amino ester)-graft-poly(ethylene glycol) amphiphilic copolymers (PAE) with phenylbutylamine functional side groups. Our report is unique in the following ways: (1) the reductively degradable micelles provide a safe and efficient doxorubicin intracellular delivery, (2) the synthesis procedure is a simple and mild pathway with a well-defined structure, and (3) the aromatic phenylbutylamine side groups increase hydrophobicity and strengthen the interaction with doxorubicin (DOX) to improve the drug-loading capability. In vitro, micelles exhibit faster release of DOX upon the action of dithiothreitol (DTT). Drug-laden micelles present higher cell inhibition efficiency in comparison to free doxorubicin, while the blank micelles show very low cytotoxicity. The copolymeric micelles show a rapid internalization and efficient cytoplasmic doxorubicin release in both human hepatocellular carcinoma HepG2 and human breast adenocarcinoma MCF-7 cell lines observed by confocal laser scanning microscopy (CLSM). The micelle is promising for enhanced intracellular drug delivery in tumour cells.
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