Hailey Sanders (University of Notre Dame)


Location: 317 DeBartolo Hall

     Biochemistry Seminar

"A Bimetallic Dual-targeting Nanoplatform for Combinational Ferroptosis Activation/Epigenetic Regulation/Photothermal Therapy Against Breast Cancer"

Abstract:  Traditional breast cancer (BC) therapies often fail to overcome cellular apoptosis resistance necessitating the development of tools to induce alternative cell death pathways including ferroptosis where complex intracellular regulation of ferroptosis limits clinical therapeutic efficiency. Combinational therapies have emerged as a tool to improve upon traditional single therapeutic outcomes but remained largely unexplored. As such, the novel nanoplatform (T-FeCo/P) was proposed as a ferroptosis inducing, epigenetic regulatory tool against BC. T-FeCo/P incorporates both iron (Fe) and cobalt (Co) to efficiently facilitate ferroptosis through encouraging Fenton/Fenton-like reactions with demonstrated increased rates of ferroptosis in 4T1 mammary cells. Furthermore, ferroptosis induction from T-FeCo/P was enriched from the light induced photothermal effect leading to increased consumption of glutathione (GSH). Co-addition of Panobinostat (Pano) synergistically promotes ferroptosis by inducing acetylation of p53 which led to downregulation of SLC7A11 and additionally decreased intracellular GSH. Collectively, the bimetallic and epigenetic regulation from T-FeCo/P disrupted intracellular ferroptosis regulation specifically by inhibition of ferroptosis suppressor, glutathione peroxidase, with intracellular GSH consumption. In-vivo use of T-FeCo/P demonstrates the therapeutic efficacy of the nanosystem with enhanced ferroptosis, suppressed tumor growth, and limited formation of metastatic nodules. These findings highlight the therapeutic potential of T-FeCo/P as BC therapy with combinational ferroptosis activation and epigenetic regulation to target intracellular ferroptosis regulatory networks.

He, Z., Zhou, H., Feng, Q., Zhang, Y., Gao, S., Liu, S., Ye, L., Ji, J., Xi, Y., Yang, X., & Zhai, G. (2024). A bimetallic dual-targeting nanoplatform for combinational ferroptosis activation/epigenetic regulation/photothermal therapy against breast cancer and tumor microenvironment remodeling. Chemical Engineering Journal, 479. https://doi.org/10.1016/j.cej.2023.147466