Systematic Surface Engineering of Magnetic Nanoworms for In vivo Tumor Targeting

Authors

  • Ji-Ho Park,

    1. Materials Science and Engineering Program Department of Chemistry and Biochemistry University of California, San Diego 9500 Gilman, La Jolla, CA 92093 (USA)
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  • Geoffrey von Maltzahn,

    1. Harvard-MIT Division of Health Sciences and Technology Massachusetts Institute of Technology 77 Massachusetts Avenue, Cambridge, MA 02139 (USA)
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  • Lianglin Zhang,

    1. Cancer Research Center Burnham Institute for Medical Research 10901 N. Torrey Pines Rd., La Jolla, CA 92037 (USA)
    2. Vascular Mapping Center Burnham Institute for Medical Research (at UCSB) Bio II Rm. #3119, University of California, Santa Barbara Santa Barbara, CA 93106 (USA)
    3. Current address: Pfizer Inc., PGRD-La Jolla 10777 Science Center Dr. San Diego, CA 92121 (USA)
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  • Austin M. Derfus,

    1. Department of Bioengineering University of California, San Diego 9500 Gilman, La Jolla, CA 92093 (USA)
    2. Current address: Biosite, Inc. 9975 Summers Ridge Road San Diego, CA 92121 (USA)
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  • Dmitri Simberg,

    1. Cancer Research Center Burnham Institute for Medical Research 10901 N. Torrey Pines Rd., La Jolla, CA 92037 (USA)
    2. Vascular Mapping Center Burnham Institute for Medical Research (at UCSB) Bio II Rm. #3119, University of California, Santa Barbara Santa Barbara, CA 93106 (USA)
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  • Todd J. Harris,

    1. Harvard-MIT Division of Health Sciences and Technology Massachusetts Institute of Technology 77 Massachusetts Avenue, Cambridge, MA 02139 (USA)
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  • Erkki Ruoslahti,

    1. Cancer Research Center Burnham Institute for Medical Research 10901 N. Torrey Pines Rd., La Jolla, CA 92037 (USA)
    2. Vascular Mapping Center Burnham Institute for Medical Research (at UCSB) Bio II Rm. #3119, University of California, Santa Barbara Santa Barbara, CA 93106 (USA)
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  • Sangeeta N. Bhatia,

    1. Harvard-MIT Division of Health Sciences and Technology Massachusetts Institute of Technology 77 Massachusetts Avenue, Cambridge, MA 02139 (USA)
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  • Michael J. Sailor

    Corresponding author
    1. Materials Science and Engineering Program Department of Chemistry and Biochemistry University of California, San Diego 9500 Gilman, La Jolla, CA 92093 (USA)
    • Materials Science and Engineering Program Department of Chemistry and Biochemistry University of California, San Diego 9500 Gilman, La Jolla, CA 92093 (USA).
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Abstract

In the design of nanoparticles that can target disease tissue in vivo, parameters such as targeting ligand density, type of target receptor, and nanoparticle shape can play an important role in determining the extent of accumulation. Herein, a systematic study of these parameters for the targeting of mouse xenograft tumors is performed using superparamagnetic iron oxide as a model nanoparticle system. The type of targeting peptide (recognizing cell surface versus extracellular matrix), the surface coverage of the peptide, its attachment chemistry, and the shape of the nanomaterial [elongated (nanoworm, NW) versus spherical (nanosphere, NS)] are varied. Nanoparticle circulation times and in vivo tumor-targeting efficiencies are quantified in two xenograft models of human tumors (MDA-MB-435 human carcinoma and HT1080 human fibrosarcoma). It is found that the in vivo tumor-targeting ability of the NW is superior to that of the NS, that the smaller, neutral CREKA targeting group is more effective than the larger, positively charged F3 molecule, that a maximum in tumor-targeting efficiency and blood half-life is observed with ≈60 CREKA peptides per NW for either the HT1080 or the MDA-MB-435 tumor types, and that incorporation of a 5-kDa polyethylene glycol linker improves targeting to both tumor types relative to a short linker. It is concluded that the blood half-life of a targeting molecule–nanomaterial ensemble is a key consideration when selecting the appropriate ligand and nanoparticle chemistry for tumor targeting.

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