BioE PhD Proposal Presentation- Alisyn Bourque
Advisors:
M.G. Finn, Ph.D. (Chemistry and Biochemistry, Georgia Institute of Technology)
Nick Housley, Ph.D., DPT, PT (Biological Sciences, Georgia Institute of Technology)
Committee:
Julie Champion, Ph.D. (Chemical and Biomolecular Engineering, Georgia Institute of Technology)
Ankur Singh, Ph.D. (Mechanical Engineering, Georgia Institute of Technology)
Timothy Cope, Ph.D. (Biological Sciences, Georgia Institute of Technology)
Exploring the Tumor Targeting Mechanism of Polymer “SANG” Nanoparticles, and Engineering SANGs for Drug Delivery to Treat Cancer
Despite substantial research into cancer therapies in the last few decades including targeted nanoparticle therapies and antibody drug conjugates, drug delivery specifically to cancer remains challenging, with less than ~1% of the injected drug dose in current cancer treatments ever getting to tumors. High chemotherapy drug doses necessary to overcome this limited delivery cause debilitating off-target toxicity in healthy tissues. A therapy that can be injected systemically and primarily target tumors without significant accumulation in healthy tissues is the main goal of cancer treatment. This work presents a novel polymer self-agglomerating nanohydrogel (SANG) that has shown significant accumulation in multiple types of solid tumors and metastases when injected systemically without any targeting ligands. SANG particles have also exhibited a unique agglomeration behavior in which above a certain concentration, the particles tend to stick to each other, forming larger aggregates. This work aims to better understand the tumor targeting capabilities and mechanism of SANGs, and exploit it by loading chemotherapeutic drugs on SANGs for application as an anti-cancer therapy. In Aim 1, the vascular mechanisms leading to SANG tumor accumulation are explored, comparing malformed, tortuous tumor vasculature to healthy vasculature. In Aim 2, chemotherapy drugs are loaded on SANGs and the anti-tumor effects of systemic administration of SANG-drugs are explored in vivo in breast and ovarian cancer models. Together, these efforts aim to advance the understanding of the tumor targeting mechanism of SANGs, and present the use of chemotherapy loaded SANGs as a novel cancer therapy for multiple types of solid tumors.