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A drug-self-gated and tumor microenvironment-responsive mesoporous silica vehicle: “four-in-one” versatile nanomedicine for targeted multidrug-resistant cancer therapy

Abstract

Design of multifunctional nanocarriers for the co-delivery of anticancer drugs and genetic agents offers an effective and promising strategy to combat multidrug resistant cancer. Herein, we developed a simple and facile way to fabricate a drug-self-gated and pH-sensitive mesoporous silica as a “four-in-one” versatile co-delivery system, which possesses targeted chemo and gene therapy capability against multidrug-resistant cancer. P-gp siRNA molecules were loaded into the channels of mesoporous silica nanoparticles. Chemotherapeutic drug (DOX) was employed as a gatekeeper via pH-sensitive benzoic–imine covalent bond. Folic acid conjugation onto the surface endowed this system excellent tumor-targeting effect, which was demonstrated by the cellular and tumor targeting assay. The effective down regulation of P-gp protein by the co-delivered P-gp siRNA was observed in western blot assay. Both in vitro cell viability study and in vivo tumor inhibition assay showed synergistic effect in suppressing cancer cell proliferation. Therefore, this drug-self-gated nanosystem exhibited great potential for the enhanced multidrug-resistant cancer treatment without any further potential risks of capping agents.

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Publication details

The article was received on 25 Jul 2017, accepted on 01 Oct 2017 and first published on 02 Oct 2017


Article type: Paper
DOI: 10.1039/C7NR05450E
Citation: Nanoscale, 2017, Accepted Manuscript
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    A drug-self-gated and tumor microenvironment-responsive mesoporous silica vehicle: “four-in-one” versatile nanomedicine for targeted multidrug-resistant cancer therapy

    W. Cheng, C. Liang, X. Wang, H. Tsai, G. Liu, Y. Peng, J. Nie, L. Huang, L. Mei and X. Zeng, Nanoscale, 2017, Accepted Manuscript , DOI: 10.1039/C7NR05450E

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