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Issue 15, 2017
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Dual-sensitive and biodegradable core-crosslinked HPMA copolymer–doxorubicin conjugate-based nanoparticles for cancer therapy

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Abstract

In this study, to increase the blood stability and circulation time of polymeric nanoparticles as well as to investigate the effects of the structure on therapeutic indexes, 2 types of N-(2-hydroxypropyl)methacrylamide (HPMA) block copolymer–doxorubicin (copolymer–DOX) conjugates, including an amphiphilic linear one and a core cross-linked one, were designed. Comparative studies on their self-assembled nanoparticles, as advanced drug delivery systems, were investigated. Both conjugates could self-assemble into polymeric nanoparticles (block copolymer-NPs and cross-linked copolymer-NPs) with sizes of ∼20 nm. Those cross-linked nanoparticles demonstrated pH-sensitive drug release features as a much higher accumulative drug release (∼80.2%) in the presence of glutathione (GSH) and pH 5.0 was observed than that in PBS (pH 7.4) without GSH (about 27.0%, 24 h). The degraded segments with low MW (MW ∼28 kDa) can be observed in the presence of a reduction agent. In addition, in vivo pharmacokinetic behaviour studies showed that the cross-linked copolymer-NPs resulted in good blood stability and long-lasting circulation time compared with the linear block copolymer-NPs and the free drug. The cell viability test and migration and invasion assay showed that both nanoparticles can inhibit cancer cell proliferation. Finally, the cross-linked copolymer-NPs exhibited the best in vivo anticancer efficacy due to the highest tumor inhibition rate of 77.75% on the A549 lung tumor model. These results suggested that cross-linked copolymer-NPs could be a potential delivery system in cancer therapy.

Graphical abstract: Dual-sensitive and biodegradable core-crosslinked HPMA copolymer–doxorubicin conjugate-based nanoparticles for cancer therapy

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Publication details

The article was received on 01 Mar 2017, accepted on 12 Mar 2017 and first published on 14 Mar 2017


Article type: Paper
DOI: 10.1039/C7PY00348J
Citation: Polym. Chem., 2017,8, 2370-2380
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    Dual-sensitive and biodegradable core-crosslinked HPMA copolymer–doxorubicin conjugate-based nanoparticles for cancer therapy

    M. Tang, M. Zhou, Y. Huang, J. Zhong, Z. Zhou and K. Luo, Polym. Chem., 2017, 8, 2370
    DOI: 10.1039/C7PY00348J

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