Event

PhD Dissertation Defense Announcement: Devorah Cahn

Thursday, May 16, 2024
10:00 a.m.
AJC 4104 (4th floor conference room)
Rachel Chang
301 405 8268
rachel53@umd.edu

Title: Overcoming the Extracellular Matrix Barrier to Nanoparticle Transport

Committee members:
Dr. Gregg A. Duncan, Chair
Dr. Matthew T. Wolf
Dr. Katharina Maisel
Dr. Hannah Zierden
Dr. Peter Kofinas, Dean's Representative

Abstract:
The extracellular matrix (ECM) is a major component of the tumor microenvironment which poses a significant barrier to nanoparticle (NP) transport, preventing delivery of therapeutic cargo. Studies have shown that PEGylation offers an effective strategy for improving NP transport in ECM. However, these studies have generally used ECM models that are not wholly representative of the native matrix. Furthermore, while ECM characteristics and composition varies across organs, it is unclear to what extent these tissue-specific characteristics affect NP transport through the ECM and how NP surface chemistry impacts ECM penetration in distinct tissues. The overall objective of this dissertation is to identify key factors of NP transport through the tumor microenvironment, facilitating the development of strategies to improve NP distribution throughout the tumor microenvironment. We hypothesize that PEG branching will enhance stability and mobility of NPs in ECM and that ECM source impacts NP transport. We further hypothesize that PEG architecture significantly affects NP mobility in ECM as well as biodistribution and tumor accumulation in vivo. We will study this through the following three aims: (1) determine the effects of PEG branching on NP stability and transport through an in vitro basement membrane model, (2) assess the impact of tissue source on NP transport through an in vitro ECM model, and (3) evaluate how PEG branching affects biodistribution, immune cell infiltration, and NP uptake in tumors in vivo. Successful completion of this work will provide additional insight into the transport mechanisms of NPs throughout the tumor microenvironment and provide additional considerations for the design of efficient NP delivery systems.