Journal
JOURNAL OF MATERIALS CHEMISTRY B
Volume 4, Issue 29, Pages 5059-5067Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c6tb01040g
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Funding
- National Natural Science Foundation of China [21274039]
- Shanghai Pujiang Program [14PJD014]
- 111 Project [B14018]
- Specialized Research Fund for the Doctoral Program of Higher Education [20130074110007]
- Basic Research Key Program Project of Commission of Science and Technology of Shanghai [12JC1403000, 12JC1403100]
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Well-defined diselenide-centered biodegradable tri-block copolymers methoxyl poly(ethylene glycol)-b-poly(epsilon-caprolactone)-b-methoxyl poly(ethylene glycol) (mPEG-PCL-Se)(2) were precisely synthesized by the combination of ring opening polymerization using di(1-hydroxyethylene) diselenide as a new initiator and a facile coupling reaction. The amphiphilic block copolymers enabled the formation of self-assembled micelles which revealed an excellent reductive response to glutathione (GSH) due to the unique reduction-responsive cleavage of the diselenide bond. Such GSH response ensured an enhanced release of anticancer drugs (DOX) from the micelles in simulative tumor microenvironments; moreover, the drug release could be changed to some extent through fine-tuning the chemical composition of the copolymers. Flow cytometry and confocal laser scanning microscopy (CLSM) measurements confirmed that the DOX-loaded micelles could be efficiently taken up by oral squamous carcinoma (HN30) cells and DOX was released into the nuclei of cancer cells following 4 h of incubation. The cell viability assays showed the diselenide-containing polymers were nontoxic up to a tested concentration (400 mu g mL(-1)), while the DOX-loaded micelles exhibited an evident inhibition toward HN30 cells. Therefore, the reduction-labile biodegradable (mPEG-PCL-Se)(2) may offer an alternative platform for tumor-targeting therapy.
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