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Issue 8, 2017
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Synergistic chemotherapeutic effect of sorafenib-loaded pullulan-Dox conjugate nanoparticles against murine breast carcinoma

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Abstract

pH-Sensitive pullulan-doxorubicin conjugates encapsulating sorafenib (P-Dox/S) nanoparticles were developed as a synergistic combinatorial delivery system against murine breast carcinoma. The nanoparticles can encapsulate Dox and sorafenib with ultra-high loading capacity (65.34 wt%) through chemical conjugation and physical loading, whereas can remain stable under physiological conditions and gradually release Dox and sorafenib with the decreasing pH. These conjugates can be effectively internalized and clearly suppress 4T1 cell growth in vitro. Furthermore, research data of in vivo animal models revealed that the synergistic combinatorial P-Dox/S nanoparticles heavily accumulated in solid tumor tissue sites to maximize therapeutic efficacy; they also significantly inhibited solid tumor growth, even remarkably reduced solid tumor volume in comparison to the initial volume, and obviously diminished adverse effects. The anti-tumor therapeutic effect obviously outperformed the delivery of combinational chemotherapy of free drugs or single drug-loaded P-Dox nanoparticles at the same concentration. These promising results indicate the high-efficiency synergistic chemotherapeutic effects of these nanoparticles. Combinational chemotherapy using P-Dox/S nanoparticles has important potential in the clinical treatment of malignancy for overcoming drug resistance and heterogeneity.

Graphical abstract: Synergistic chemotherapeutic effect of sorafenib-loaded pullulan-Dox conjugate nanoparticles against murine breast carcinoma

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The article was received on 14 Dec 2016, accepted on 13 Jan 2017 and first published on 16 Jan 2017


Article type: Paper
DOI: 10.1039/C6NR09639E
Nanoscale, 2017,9, 2755-2767

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    Synergistic chemotherapeutic effect of sorafenib-loaded pullulan-Dox conjugate nanoparticles against murine breast carcinoma

    J. Sui, Y. Cui, H. Cai, S. Bian, Z. Xu, L. Zhou, Y. Sun, J. Liang, Y. Fan and X. Zhang, Nanoscale, 2017, 9, 2755
    DOI: 10.1039/C6NR09639E

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