Engineering Targeted Therapeutics for Triple Negative Breast Cancer
Monday, November 9, 2020
The fundamental goal of my research is to advance the rational design of targeted drug delivery vehicles based on exploiting chemical and mechanical properties. My research program seeks to understand how molecular patterns govern cellular function and to use biomimicry to design nanoparticles to target and eradicate cancer cells. My research challenges traditional conventions in targeted drug delivery by focusing on specific physical attributes of the nanoparticle. These attributes can be measured quantitatively and tested in vivo for their impact on tumor accumulation and therapeutic efficacy. First, we have engineered temporal and spatial molecular patterns that recognize target cells. Instead of targeting a single overexpressed receptor, we design nanoparticles that cooperatively bind multiple receptors by optimizing the ratios and surface density to precisely-match cell expression. Second, cell receptors are not static, they change with time and upon exposure to chemical cues. Therefore, cells may be targeted based on their microenvironment. We have demonstrated how cytokine activation and lipid diffusivity alter nanoparticle-cell adhesion. Using atomic force microscopy, we measured binding force interactions between live cancer cells and functionalized surfaces, which predicted in vivo tumor targeting. Third, nanoparticles, like cells, can squeeze through endothelial cell junctions. We have demonstrated that nanoparticle elasticity directs tumor accumulation. My lab identifies quantitative design criteria to engineer nanoparticles that recognize cancer cells and their environments.
Debra Auguste, PhD is a Professor of Chemical Engineering at Northeastern University. She received her S.B. in Chemical Engineering from MIT in 1999 and her Ph.D. in Chemical Engineering from Princeton University in 2005. She was trained as a Post-Doctoral Associate at MIT. Her interests include drug and gene delivery, targeted drug delivery, stimuli sensitive materials. Dr. Auguste is the principal investigator on grants from the National Institute of Health (NIH), Office of Naval Research (ONR), Defense Advanced Research Projects Agency (DARPA), National Science Foundation (NSF), and the Juvenile Diabetes Research Foundation (JDRF). She is a recipient of various awards including: the Presidential Early Career in Science and Engineering, the NIH Director’s New Innovator, NSF CAREER Award, and the DARPA Young Faculty Award. Dr. Auguste was elected as a Fellow of the Biomedical Engineering Society and American Institute of Medical and Biological Engineering.