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Synthesis of Biomolecule-Modified Mesoporous Silica Nanoparticles for Targeted Hydrophobic Drug Delivery to Cancer Cells

Authors

  • Daniel P. Ferris,

    1. Department of Chemistry and Biochemistry, University of California, Los Angeles, 405 Hilgard Avenue, Los Angeles, California 90095–1569, USA, Tel: (+1)-310–825-1001; Fax: (+1)-310–206-4038
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  • Jie Lu,

    1. Department of Microbiology, Immunology and and Molecular Genetics, University of California, Los Angeles, 405 Hilgard Avenue, Los Angeles, California 90095–1569, USA, Tel: (+1)-310–206-7318; Fax: (+1)-310–206-5231
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  • Chris Gothard,

    1. Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208, USA
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  • Rolando Yanes,

    1. Department of Microbiology, Immunology and and Molecular Genetics, University of California, Los Angeles, 405 Hilgard Avenue, Los Angeles, California 90095–1569, USA, Tel: (+1)-310–206-7318; Fax: (+1)-310–206-5231
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  • Courtney R. Thomas,

    1. Department of Chemistry and Biochemistry, University of California, Los Angeles, 405 Hilgard Avenue, Los Angeles, California 90095–1569, USA, Tel: (+1)-310–825-1001; Fax: (+1)-310–206-4038
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  • John-Carl Olsen,

    1. Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208, USA
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  • J. Fraser Stoddart,

    1. Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208, USA
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  • Fuyuhiko Tamanoi,

    Corresponding author
    1. Department of Microbiology, Immunology and and Molecular Genetics, University of California, Los Angeles, 405 Hilgard Avenue, Los Angeles, California 90095–1569, USA, Tel: (+1)-310–206-7318; Fax: (+1)-310–206-5231
    • Department of Microbiology, Immunology and and Molecular Genetics, University of California, Los Angeles, 405 Hilgard Avenue, Los Angeles, California 90095–1569, USA, Tel: (+1)-310–206-7318; Fax: (+1)-310–206-5231.
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  • Jeffrey I. Zink

    Corresponding author
    1. Department of Chemistry and Biochemistry, University of California, Los Angeles, 405 Hilgard Avenue, Los Angeles, California 90095–1569, USA, Tel: (+1)-310–825-1001; Fax: (+1)-310–206-4038
    • Department of Chemistry and Biochemistry, University of California, Los Angeles, 405 Hilgard Avenue, Los Angeles, California 90095–1569, USA, Tel: (+1)-310–825-1001; Fax: (+1)-310–206-4038
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Abstract

Synthetic methodologies integrating hydrophobic drug delivery and biomolecular targeting with mesoporous silica nanoparticles are described. Transferrin and cyclic-RGD peptides are covalently attached to the nanoparticles utilizing different techniques and provide selectivity between primary and metastatic cancer cells. The increase in cellular uptake of the targeted particles is examined using fluorescence microscopy and flow cytometry. Transferrin-modified silica nanoparticles display enhancement in particle uptake by Panc-1 cancer cells over that of normal HFF cells. The endocytotic pathway for these particles is further investigated through plasmid transfection of the transferrin receptor into the normal HFF cell line, which results in an increase in particle endocytosis as compared to unmodified HFF cells. By designing and attaching a synthetic cyclic-RGD, selectivity between primary cancer cells (BT-549) and metastatic cancer cells (MDA-MB 435) is achieved with enhanced particle uptake by the metastatic cancer cell line. Incorporation of the hydrophobic drug Camptothecin into these two types of biomolecular-targeted nanoparticles causes an increase in mortality of the targeted cancer cells compared to that caused by both the free drug and nontargeted particles. These results demonstrate successful biomolecular-targeted hydrophobic drug delivery carriers that selectively target specific cancer cells and result in enhanced drug delivery and cell mortality.

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