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Mesoporous Silica Nanoparticles for Cancer Therapy: Energy-Dependent Cellular Uptake and Delivery of Paclitaxel to Cancer Cells
Authors:Jie Lu  Monty Liong  Sean Sherman  Tian Xia  Michael Kovochich  Andre E. Nel  Jeffrey I. Zink  Fuyuhiko Tamanoi
Affiliation:(1) Department of Microbiology, Immunology and Molecular Genetics, Jonsson Comprehensive Cancer Center, Molecular Biology Institute, University of California Los Angeles, 405 Hilgard Avenue, Los Angeles, CA 90095, USA;(2) Department of Chemistry and Biochemistry, University of California Los Angeles, 405 Hilgard Avenue, Los Angeles, CA 90095, USA;(3) Department of Medicine, University of California Los Angeles, 405 Hilgard Avenue, Los Angeles, CA 90095, USA;(4) California NanoSystems Institute, University of California Los Angeles, 405 Hilgard Avenue, Los Angeles, CA 90095, USA;(5) Department of Microbiology, Immunology and Molecular Genetics, California NanoSystems Institute, JCCC, University of California Los Angeles, 405 Hilgard Avenue, Los Angeles, CA 90095, USA
Abstract:
Biocompatible mesoporous silica nanoparticles, containing the fluorescence dye fluorescein isothiocyanate (FITC), provide a promising system to deliver hydrophobic anticancer drugs to cancer cells. In this study, we investigated the mechanism of uptake of fluorescent mesoporous silica nanoparticles (FMSN) by cancer cells. Incubation with FMSN at different temperatures showed that the uptake was higher at 37°C than at 4°C. Metabolic inhibitors impeded uptake of FMSN into cells. The inhibition of FMSN uptake by nocodazole treatment suggests that microtubule functions are required. We also report utilization of mesoporous silica nanoparticles to deliver a hydrophobic anticancer drug paclitaxel to PANC-1 cancer cells and to induce inhibition of proliferation. Mesoporous silica nanoparticles may provide a valuable vehicle to deliver hydrophobic anticancer drugs to human cancer cells.
Keywords:mesoporous silica nanoparticle  endocytosis  hydrophobic drugs  drug delivery  cancer
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