Co-delivery of doxorubicin and Bcl-2 siRNA by mesoporous silica nanoparticles enhances the efficacy of chemotherapy in multidrug-resistant cancer cells.
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ABSTRACT:
SUBMITTER: Chen AM
PROVIDER: S-EPMC2833276 | biostudies-literature | 2009 Dec
REPOSITORIES: biostudies-literature
Publications
Co-delivery of doxorubicin and Bcl-2 siRNA by mesoporous silica nanoparticles enhances the efficacy of chemotherapy in multidrug-resistant cancer cells.
Chen Alex M AM Zhang Min M Wei Dongguang D Stueber Dirk D Taratula Oleh O Minko Tamara T He Huixin H
Small (Weinheim an der Bergstrasse, Germany) 20091201 23
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Project description:BackgroundEffective gastric carcinoma (GC) chemotherapy is subject to many in vitro and in vivo barriers, such as tumor microenvironment and multidrug resistance.Materials and methodsHerein, we developed a hyaluronic acid (HA)-modified silica nanoparticle (HA-SiLN/QD) co-delivering quercetin and doxorubicin (DOX) to enhance the efficacy of GC therapy (HA-SiLN/QD). The HA modification was done to recognize overexpressed CD44 receptors on GC cells and mediate selective tumor targeting. In parallel, quercetin delivery decreased the expression of Wnt16 and P-glycoprotein, thus remodeling the tumor microenvironment and reversed multidrug resistance to facilitate DOX activity.ResultsExperimental results demonstrated that HA-SiLN/QD was nanoscaled particles with preferable stability and sustained release property. In vitro cell experiments on SGC7901/ADR cells showed selective uptake and increased DOX retention as compared to the DOX mono-delivery system (HA-SiLN/D).ConclusionIn vivo anticancer assays on the SGC7901/ADR tumor-bearing mice model also revealed significantly enhanced efficacy of HA-SiLN/QD than mono-delivery systems (HA-SiLN/Q and HA-SiLN/D).
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Project description:PurposeTo prepare mesoporous silica-based delivery systems capable of simultaneous delivery of drugs and nucleic acids.MethodsThe surface of mesoporous silica nanoparticles (MSN) was modified with poly(ethylene glycol) (PEG) and poly(2-(dimethylamino)ethylmethacrylate) (PDMAEMA) or poly(2-(diethylamino)ethylmethacrylate) (PDEAEMA). The particles were then loaded with a lysosomotropic agent chloroquine (CQ) and complexed with plasmid DNA or siRNA. The ability of the synthesized particles to deliver combinations of CQ and nucleic acids was evaluated using luciferase plasmid DNA and siRNA targeting luciferase and GAPDH.ResultsThe results show a slow partial MSN dissolution to form hollow silica nanoparticles in aqueous solution. The biological studies show that polycation-modified MSN are able to simultaneously deliver CQ with DNA and siRNA. The co-delivery of CQ and the nucleic acids leads to a significantly increased transfection and silencing activity of the complexes compared with MSN not loaded with CQ.ConclusionPEGylated MSN modified with polycations are promising delivery vectors for combination drug/nucleic acid therapies.
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