Date(s) - 03/09/2020
3:00 pm - 4:00 pm
Molecular engineering of multifunctional, multivalent micelles provides a tool for the detection and targeted delivery of therapeutics to diseases including cardiovascular and chronic kidney disease. Moreover, through rational design, these nanoparticles have the potential to deliver signals to report back on or influence the regeneration of the cellular niche for personalized medicine regimes, while addressing the limitations of current clinical diagnostic and therapeutic strategies. To this end, we have engineered multimodal micelles that can harness clearance mechanisms and bind to various markers of diseases for therapeutic and diagnostic applications.
For kidney diseases, while small molecule drugs have been proposed as a therapy to manage disease progression, high dosages are often required to achieve therapeutic efficacy, generating off-target side effects, some of which are lethal. To address these limitations, our lab has designed a novel, kidney-targeting peptide amphiphile micelle (KPAM) system toward drug delivery applications. Specifically, KPAMs were found to cross the glomerular filtration barrier and bind to megalin, a multiligand cell surface receptor present on renal tubule cells. When incubated with human kidney proximal tubule cells, KPAMs were found to be biocompatible in vitro and showed higher accumulation in kidneys compared to nontargeted controls in vivo. We provide proof-of-concept studies for their utility in autosomal polycystic kidney disease and their application using various routes of administration.
In addition, due to the modularity of PAMs and their potential for theranostic (“thera”-peutic + “diag”-nostic) applications, I will also present our efforts in developing microRNA nanotherapeutics for calcification and smooth muscle cell targeting to detect and inhibit atherosclerosis. Such micelles have the potential to be the next generation of nanoparticles with capabilities to bind to specific disease markers of interest, deliver a therapeutic, and monitor the progression and regression of the disease in real-time.
Eun Ji Chung is an Assistant Professor in the Department of Biomedical Engineering at the University of Southern California and the Karl Jacobs Jr. and Karl Jacobs III Early Career Chair. She has a courtesy appointment in Chemical Engineering, Medicine (Nephrology and Hypertension), and Surgery (Vascular Surgery and Endovascular Repair), and is an affiliated faculty at the Norris Cancer Center and the Stem Cells department. Her laboratory is interested in harnessing molecular design and self-assembly to develop nano- to macroscale biomaterials that can be utilized in medicine. Dr. Chung received her B.A. with honors in Molecular Biology from Scripps College, her Ph.D. from the Department of Biomedical Engineering from Northwestern University, and her postdoctoral training from the Institute for Molecular Engineering at the University of Chicago. Dr. Chung is a recipient of the NIH K99/R00 Pathway to Independence Award (2014) and the NIH Director’s New Innovator Award (DP2, 2018), and was named 35 Under 35 from the American Institute of Chemical Engineers (2017), an Emerging Investigator in Biomaterials Science (2017), Young Innovator in Nanobiotechnology from Nano Research (2018), Emerging Investigator from the Journal of Materials Chemistry B (2019), New Innovator from IEEE-Nanomed (2019), and Rising Star in Cellular and Molecular Bioengineering from BMES (2020). She also received the USC faculty mentoring award for undergraduates in 2018. Dr. Chung is an Associate Editor for the journals Bioactive Materials and Frontiers in Digital Health and Health Technologies.