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

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

Nanoscale. 2017 Oct 31;:

Authors: Cheng W, Liang C, Wang X, Tsai HI, Liu G, Peng Y, Nie J, Huang L, Mei L, Zeng X

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.

PMID: 29085938 [PubMed - as supplied by publisher]

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