Tumor heterogeneity can significantly influence the efficacy of cancer chemotherapy and nanoparticle-mediated drug delivery. Therefore, there is a need of multifunctional nanoparticles that can deliver therapeutics and be tracked longitudinally. The research described in this thesis explores magnetic nanoparticles for applications in tumor identification, monitoring nanoparticle biodistribution, and cancer therapy. The multifunctional formulation can potentially be used in image-guided drug therapy to enhance diagnostic procedures and therapeutic outcomes.
The magnetic nanoparticle formulation consists of an iron-oxide magnetic core coated with oleic acid then stabilized with an amphiphilic block copolymer. Magnetic nanoparticles coated with the copolymer Pluronic F127 demonstrate sustained and enhanced magnetic resonance contrast in the whole tumor of a mouse breast xenograft tumor model. Hydrophobic near infrared dyes were loaded into the oleic acid coating of the magnetic nanoparticles to quantitatively determine their long-term biodistribution in vivo. The magnetic nanoparticles are visible in orthotopic breast tumors up to 12 days post-injection through in vivo fluorescence imaging. One-hour exposure to a magnetic field further enhances magnetic nanoparticle localization to the tumors.
The anticancer drugs doxorubicin and paclitaxel were loaded into the oleic acid layer of the magnetic nanoparticles for therapeutic treatment of breast cancer. Drug loaded magnetic nanoparticles effectively treat breast cancer cells in vitro, while plain magnetic nanoparticles are non-toxic. Both plain and drug loaded magnetic nanoparticles significantly decrease tumor size and increase survival in tumor bearing mice compared to saline controls. Plain magnetic nanoparticles localized in the tumor as they breakdown may generate reactive oxygen species due to the Fenton reaction, causing apoptosis of cancer cells and leading to therapeutic effect without drug. The magnetic nanoparticles
have the potential to be developed as an effective cancer theranostic agent, i.e., an agent with combined imaging and therapeutic applications.