Mesoporous Silica Nanoparticles for Cancer Therapy: Energy-Dependent Cellular Uptake and Delivery of Paclitaxel to Cancer Cells

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.

[1]  Mette Ebbesen,et al.  Nanomedicine: Techniques, Potentials, and Ethical Implications , 2006, Journal of biomedicine & biotechnology.

[2]  Victor S-Y Lin,et al.  Effect of surface functionalization of MCM-41-type mesoporous silica nanoparticles on the endocytosis by human cancer cells. , 2006, Journal of the American Chemical Society.

[3]  A. Reynolds,et al.  Nanoparticle-mediated gene delivery to tumour neovasculature. , 2003, Trends in Molecular Medicine.

[4]  Galen D. Stucky,et al.  MESOPOROUS SILICATE SEQUESTRATION AND RELEASE OF PROTEINS , 1999 .

[5]  A. McPhail,et al.  Plant antitumor agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. , 1971, Journal of the American Chemical Society.

[6]  Chung-Yuan Mou,et al.  The effect of surface charge on the uptake and biological function of mesoporous silica nanoparticles in 3T3-L1 cells and human mesenchymal stem cells. , 2007, Biomaterials.

[7]  H. Lichstein,et al.  Studies of the Effect of Sodium Azide on Microbic Growth and Respiration , 1944, Journal of bacteriology.

[8]  P. Milkiewicz,et al.  Control by signaling modulators of the sorting of canalicular transporters in rat hepatocyte couplets: Role of the cytoskeleton , 2000, Hepatology.

[9]  L. Brannon-Peppas,et al.  Nanoparticle and targeted systems for cancer therapy. , 2004, Advanced drug delivery reviews.

[10]  Julia Xiaojun Zhao,et al.  Toxicity of luminescent silica nanoparticles to living cells. , 2007, Chemical research in toxicology.

[11]  J. Heuser,et al.  Hypertonic media inhibit receptor-mediated endocytosis by blocking clathrin-coated pit formation , 1989, The Journal of cell biology.

[12]  S. Maddrell,et al.  H + V-ATPases Energize Animal Plasma Membranes for Secretion and Absorption of Ions and Fluids' , 1998 .

[13]  Kemin Wang,et al.  Uptake of silica-coated nanoparticles by HeLa cells. , 2005, Journal of nanoscience and nanotechnology.

[14]  R. Himes,et al.  Nocodazole action on tubulin assembly, axonal ultrastructure and fast axoplasmic transport. , 1979, The Journal of pharmacology and experimental therapeutics.

[15]  W. Mark Saltzman,et al.  Enhancement of transfection by physical concentration of DNA at the cell surface , 2000, Nature Biotechnology.

[16]  R. Crowther,et al.  Structure and assembly of coated vesicles. , 1987, Annual review of biophysics and biophysical chemistry.

[17]  J. S. Beck,et al.  Ordered mesoporous molecular sieves synthesized by a liquid-crystal template mechanism , 1992, Nature.

[18]  J. W. Chen,et al.  Isolation and sequencing of a cDNA clone encoding lysosomal membrane glycoprotein mouse LAMP-1. Sequence similarity to proteins bearing onco-differentiation antigens. , 1988, The Journal of biological chemistry.

[19]  Monty Liong,et al.  Mesoporous silica nanoparticles as a delivery system for hydrophobic anticancer drugs. , 2007, Small.

[20]  Dan Luo,et al.  Cellular Fate of a Modular DNA Delivery System Mediated by Silica Nanoparticles , 2008, Biotechnology progress.

[21]  Mansoor M Amiji,et al.  Multi-functional polymeric nanoparticles for tumour-targeted drug delivery , 2006, Expert opinion on drug delivery.

[22]  P. G. Canonico,et al.  THE USE OF ACRIDINE ORANGE AS A LYSOSOMAL MARKER IN RAT SKELETAL MUSCLE , 1969, The Journal of cell biology.

[23]  Jun-Sung Kim,et al.  Cellular uptake of magnetic nanoparticle is mediated through energy-dependent endocytosis in A549 cells , 2006, Journal of veterinary science.