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Gold Nanoparticles as Drug Delivery Vectors for Photodynamic Therapy of Cancers

Cheng, Yu
http://rave.ohiolink.edu/etdc/view?acc_num=case1301503263

Abstract Details

2011, Doctor of Philosophy, Case Western Reserve University, Chemistry.
Gold nanoparticle-drug conjugates have attracted increasing attention in drug delivery for photodynamic cancer therapy. The nanoparticle acts as a water-soluble and bio-compatible platform that allows the delivery of hydrophobic drugs to the site of therapy. Due to the favorable surface area, hundreds of molecules can be attached to a 5 nm gold nanoparticle. More importantly, the versatile nanoparticle surface plays a vital role in targeted drug delivery. In this dissertation, we focus on efficient drug vectors for cancer therapy by synthesizing PEGylated gold nanoparticle-phthalocyanine conjugates. Both covalent and non-covalent drug binding can be achieved by designing the functionality of the nanoparticle surface. Due to the design of the gold nanoparticle carrier, using amphiphilic polymers, the drug delivery can be facilitated based on its size and the enhanced permeability and retention in the tumor tissue. Compared to the covalent approach, the non-covalent delivery approach of the hydrophobic photodynamic therapy drug Pc 4 through gold nanoparticles has provided rapid release and enhanced photocytotoxicity in cancer cells. In vivo studies in cancer bearing mice have shown an efficient deep penetration of the drug into the target tumors by the nanoparticle carriers within hours. In addition, controlled drug delivery system using visible-NIR light is achieved by a masked Pc 4-gold nanoparticle conjugate system. Targeted drug delivery can be achieved by modification of the carrier surface with active targeting ligands. After modification of the gold nanoparticle-Pc 4 conjugates with an EGF peptide, drug uptake into the tumor cells is dramatically improved due to the combination of active and passive targeting compared to untargeted conjugates. A 10-fold increase of the drug accumulation in a brain tumor was observed for the targeted drug delivery system. This shows that the designed gold nanoparticle-based drug delivery vector is able to cross the blood brain tumor barrier to address the brain tumor owning to the EGF targeted effect. The biodistribution of the drug and gold nanoparticles in vivo was investigated over a time frame of seven days. The biodistribution of the drug was studied by monitoring its intrinsic fluorescence in the organs and the gold nanoparticle concentrations in the corresponding organs have been quantified as well. Both gold nanoparticles and the drug can be removed from the body through renal clearance and the hepatobiliary system within days after drug administration.
Clemens Burda (Advisor)
Robert Salomon (Committee Chair)
Malcolm Kenney (Committee Member)
Yanming Wang (Committee Member)
James Basilion (Committee Member)
209 p.
Chemistry
gold nanoparticles; drug delivery; cancer; photodynamic therapy; targeted drug delivery

Recommended Citations

Citations

  • Cheng, Y. (2011). Gold Nanoparticles as Drug Delivery Vectors for Photodynamic Therapy of Cancers [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1301503263

    APA Style (7th edition)

  • Cheng, Yu. Gold Nanoparticles as Drug Delivery Vectors for Photodynamic Therapy of Cancers. 2011. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1301503263.

    MLA Style (8th edition)

  • Cheng, Yu. "Gold Nanoparticles as Drug Delivery Vectors for Photodynamic Therapy of Cancers." Doctoral dissertation, Case Western Reserve University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=case1301503263

    Chicago Manual of Style (17th edition)

case1301503263
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© 2011, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.