Journal
NANOSCALE
Volume 9, Issue 43, Pages 17063-17073Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c7nr05450e
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Funding
- National Natural Science Foundation of China [81771966, 51703258, 81641051]
- Guangdong Natural Science Funds for Distinguished Young Scholar [2014A030306036]
- Science and Technology Planning Project of Guangdong Province [2016A020217001]
- Natural Science Foundation of Guangdong Province [2015A030313848]
- Science, Technology & Innovation Commission of Shenzhen Municipality [JCYJ20160301152300347, JCYJ20160531195129079, JCYJ20170412095722235, JCYJ20140418112611757, ZDSYS20140509172959975, GJHZ20140416153844269]
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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.
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