Journal
RSC ADVANCES
Volume 7, Issue 48, Pages 30242-30249Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c7ra04254j
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Funding
- Natural Science Foundation of Tianjin [14JCYBJC18100]
- NSFC [51203079]
- PCSIRT [IRT1257]
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A pH- and reduction-responsive anticancer drug delivery system was prepared and the triggerable and controllable drug release in response to stimuli was observed. In the first step, methoxy-poly(ethylene glycol) (mPEG) was conjugated with polysuccinimide (PSI) via disulfide linkages, and the PSI segment thereafter, was aminolyzed by 2-diisopropylaminoethylamine (DIPEA) and hydrazine hydrate (Hy). The obtained amphiphilic copolymer could form a bond with the model drug doxorubicin (DOX) at pH 7.4 via acid-labile hydrazone bonds, and more free DOX molecules could be encapsulated via hydrophobic interactions and p-p stacking between the aromatic rings, leading to DOX-loaded micelles formation. These polymers and polymeric micelles then were characterized. The results showed that the polymeric micelles exhibited dual pH-and reduction-responsive disassembly behaviors. Moreover, while the blank copolymers had excellent cytocompatibility, the DOX-loaded micelles showed an enhanced drug release profile and improved cytotoxicity with decrease of pH and/or the addition of glutathione (GSH). These results indicated that the novel nanoparticle based on PEG-SS-poly(amino acid) block copolymer is a promising candidate for a carrier in controllable anti-tumor drug delivery.
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