Issue 43, 2017

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

Abstract

The 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 method to fabricate a drug-self-gated and pH-sensitive mesoporous silica vehicle 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. A chemotherapeutic drug (DOX) was employed as a gatekeeper via a pH-sensitive benzoic–imine covalent bond. Folic acid conjugation onto the surface endowed this system with an excellent tumor-targeting effect, which was demonstrated by the cellular and tumor targeting assay. The effective downregulation of P-gp protein by the co-delivered P-gp siRNA was observed by western blotting. Both the in vitro cell viability study and in vivo tumor inhibition assay showed a synergistic effect in suppressing cancer cell proliferation. Therefore, this drug-self-gated nanosystem exhibited great potential for improved multidrug-resistant cancer treatment without any further potential risks of capping agents.

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

Supplementary files

Article information

Article type
Paper
Submitted
25 Jul 2017
Accepted
01 Oct 2017
First published
02 Oct 2017

Nanoscale, 2017,9, 17063-17073

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, 9, 17063 DOI: 10.1039/C7NR05450E

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