Journal
RSC ADVANCES
Volume 4, Issue 22, Pages 11089-11098Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c3ra46914j
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Funding
- National Science Foundation of Taiwan [NSC-100-2320-B-037-003-MY3, NSC 101-2325-B037-006, NSC 102-2325-B037-005]
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A star-shaped poly(3-caprolactone)-b-poly(dimethylaminoethyl methacrylate) copolymer (S-PCL-PDMAEMA) was synthesized and applied to co-deliver pDNA and doxorubicin (DOX) into cancer cells. A linear-shaped L-PCL-PDMAEMA was prepared for comparison. A star-shaped PCL homopolymer (S-PCL) was synthesized through a ring-opening reaction of 3-caprolactone with pentaerythritol, followed by brominating the end hydroxyl groups of S-PCL to yield S-PCL-Br. The S-PCL-PDMAEMA was obtained via atom transfer radical polymerization using DMAEMA as a monomer and S-PCL-Br as a macroinitiator. Similar numbers of repeating units of PCL and PDMAEMA were controlled for L-PCL-PDMAEMA and S-PCL-PDMAEMA. The star-shaped copolymer formed uniform nano-sized micelles in water with lower cytotoxicity than the linear one and PDMAEMA. The L-PCL-PDMAEMA and S-PCL-PDMAEMA effectively formed polyplexes with pDNA at a low N/P ratio. The DOX-loaded S-PCL-PDMAEMA micelles showed a better cell-killing effect than the DOX-loaded L-PCL-PDMAEMA in four cell lines. The co-delivery of DOX and pDNA was confirmed using a confocal laser scanning microscope. The S-PCL-PDMAEMA delivered the drugs into the nuclei of U87 cells for 3 h of incubation but the L-PCL-PDMAEMA accumulated most of them in the cytoplasm. This result demonstrated the cationic S-PCL-PDMAEMA micelles are a promising co-delivery system for therapeutic pDNA and hydrophobic anticancer drugs.
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