This proposal combines fluorescent imaging, active targeting, and subsequent photothermal treatment of malignant cells as an approach for treating head and neck cancers. The use of a near-infrared (NIR) laser enables us to take advantage of both the plasmon resonance absorption peak of gold nanorods (AuNRs), ~785 nm, as well as the absorption peak of the fluorescent dye, ~774 nm. We propose to label anti-EGFR antibodies, which target the over-expressed EGFR on malignant cells, with a fluorescent dye and conjugate them to AuNRs. This active targeting is expected to prove more efficient than previously reported approaches that relied solely on enhanced permeability and retention effects. Our preliminary results suggest that NIR photothermal treatment heated the AuNRs, excited fluorescence, killed approximately 90% of tumor cells in vitro, and provided a 40% reduction in tumor volume in vivo. To our knowledge, this is the first demonstration of a minimally invasive modality to combine tumor targeting and fluorescent imaging with a method to induce tumor regression in live mice.
We aim to demonstrate that this multifunctional platform to target, image, and treat tumors is an improvement over current treatment regimens for Veterans suffering with head and neck cancer.
A cheaper, faster, and more specific cancer treatment would save the Veterans Administration (VA) money, time, and lives. Improvement is needed, especially for patients with regionally advanced, recurrent, chemo-resistant, or stage IV cancer and during palliative care. Targeted specificity of antibody-based therapies, combined with fluorescent imaging and the tumor regression induced by photo-thermal therapy, could improve side effects and tumor cell kill rates. This proposal investigates how fluorescently-labeled antibodies improve imaging and the targeted delivery of laser-activated nanoparticles and how these nanoparticles enhance the therapeutic efficacy of the antibody therapy. This represents a new class of adjuvant therapies. The broader impact may include shorter treatment times, cheaper costs, and decreased side effects, leading to improved patient prognosis, quality of life, and life span for Veterans.
