Reduction-Responsive Amphiphilic Star Copolymers with Long-chain Hyperbranched Poly(ε-caprolactone) Core and Disulfide Bonds for Trigger Release of Anticancer Drugs

Zhang, Shan, Hou, Yinglai, Chen, Heng, Liao, Zijun, Chen, Jianxin, Xu, Bin and Kong, Jie (2018) Reduction-Responsive Amphiphilic Star Copolymers with Long-chain Hyperbranched Poly(ε-caprolactone) Core and Disulfide Bonds for Trigger Release of Anticancer Drugs. European Polymer Journal, 108. pp. 364-372. ISSN 0014-3057

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Abstract

In this contribution, the reduction-responsive star copolymers with long-chain hyperbranched poly(ε-caprolactone) (PCL) (HyperMacs) core and disulfide bonds were synthesized via Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. The HyperMacs core was constructed from disulfide-containing AB2-type PCL macromonomers, which possesses length-adjustable chain segments between branching points, large cavities, low degree of crystallinity, and reduction-responsivity. After grafted with poly(ethylene glycol), the reduction-responsive star copolymers can self-assemble into micelles in aqueous solution. The obtained micelles exhibited much lower critical micelle concentration (CMC) than their linear analogues. The reduction-responsivity from disulfide bonds makes them a promising carrier candidate for trigger release of anticancer drugs. The in vitro release results confirmed that their doxorubicin (DOX)-loaded micelles exhibited desirable reduction-triggered release performance. The cellular proliferation inhibition against HepG2 cells demonstrated that the DOX-loaded micelles showed a comparable anticancer activity with free DOX. Therefore, it can be expected that the reduction-sensitive micelles may serve as smart vehicles for intracellular delivery of anti-cancer drugs in tumour therapy.

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