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  • Title: Reduction-sensitive micelles with sheddable PEG shells self-assembled from a Y-shaped amphiphilic polymer for intracellular doxorubicine release.
    Author: Cui C, Yu P, Wu M, Zhang Y, Liu L, Wu B, Wang CX, Zhuo RX, Huang SW.
    Journal: Colloids Surf B Biointerfaces; 2015 May 01; 129():137-45. PubMed ID: 25843367.
    Abstract:
    A new type of shell-sheddable micelles with disulfide linkages between the hydrophobic polyester core and hydrophilic poly(ethylene glycol) (PEG) shell was developed based on Y-shaped amphiphilic polymers mPEG-S-S-(PCL)2. The micelles were then used for the glutathione-mediated intracellular delivery of the anticancer drug doxorubicin (DOX) into tumor cells. The polymer could self-assemble into micelles with an average diameter of 135nm in aqueous solution and load DOX at a total content of 3.6%. The hydrophilic PEG shell of these micelles could be shed in the presence of reducing agent dithiothreitol (DTT), which resulted in size change of the micelles. In vitro release studies revealed that DOX-loaded mPEG-S-S-(PCL)2 micelles exhibited faster DOX release in the presence of DTT. MTT assay demonstrated that DOX-loaded mPEG-S-S-(PCL)2 micelles showed higher cytotoxicity against 10mM of glutathione monoester (GSH-OEt) pretreated HeLa cells than that of the non-pretreated ones. Confocal laser scanning microscopy and flow cytometry analyses indicated that DOX-loaded mPEG-S-S-(PCL)2 micelles were efficiently internalized into HeLa cells and exhibited faster DOX release in GSH-OEt-pretreated cells than in cells with no pretreatment. Endocytosis inhibition results proved that mPEG-S-S-(PCL)2 micelles entered the cells mainly through the clathrin-mediated endocytosis pathway, and caveolae-mediated endocytosis was involved to a small extent. These results indicate the great potential of the proposed Y-shaped reduction-sensitive polymer for application in effective intracellular anticancer drug delivery.
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