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Issue 3, 2013
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Novel shell-cross-linked micelles with detachable PEG corona for glutathione-mediated intracellular drug delivery

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Abstract

A series of novel disulfide-containing triblock copolymers, poly(ethylene glycol)-b-poly(L-lysine)-b-poly(rac-leucine) (PEG-SS-PLys-PLeu), were prepared. In an aqueous solution, the copolymers could self-assemble to form core–shell-corona micelles with a disulfide-linked detachable PEG corona, since the PLys middle shell with primary amine groups was linked by a disulfide-containing cross-linker. The morphology and stability of self-assembled micelles were characterized by TEM, DLS and SEM. In the intracellular environment, the micelles underwent destruction of the cross-linked shell with detachment of the PEG corona due to the cleavage of disulfide bonds, followed by the collapse of micelles. The in vitro drug release in response to GSH was further studied. Interestingly, it was found that the micelles not only exhibited reduced drug loss in extracellular environments, but also drastically accelerated drug release at the cytoplasmic GSH level, leading to enhanced growth inhibition of HeLa cells. The glutathione-responsive micelles might have great potential in intracellular drug delivery.

Graphical abstract: Novel shell-cross-linked micelles with detachable PEG corona for glutathione-mediated intracellular drug delivery

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Publication details

The article was received on 02 Sep 2012, accepted on 17 Oct 2012 and first published on 02 Nov 2012


Article type: Paper
DOI: 10.1039/C2SM27028E
Soft Matter, 2013,9, 692-699

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    Novel shell-cross-linked micelles with detachable PEG corona for glutathione-mediated intracellular drug delivery

    K. Wang, Y. Liu, W. Yi, C. Li, Y. Li, R. Zhuo and X. Zhang, Soft Matter, 2013, 9, 692
    DOI: 10.1039/C2SM27028E

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