University of Maryland,
Keywords: drug delivery, biomaterials
Summary:Physiological transport of fluid, molecules, proteins, and cells throughout the body is critical for homeostasis. While transport processes like cell migration and molecular passage across cellular barriers are well documented, less is known about transport across the interstitial tissue spaces and into lymphatic vessels. Lymphatic vessels are critical for maintenance of tissue homeostasis and forming the adaptive immune response, as they are the natural conduit between peripheral tissues and the lymph nodes (LNs), where the immune response is shaped. Because particulates are primarily shuttled via lymphatic vessels, lymphatics have received considerable attention in recent years as potential targets for drug delivery, particularly for immune modulation. Transport across interstitial tissue governs what enters lymphatic vessels vs. blood vessels and thus understanding extracellular tissues is vital to design therapeutics. However, we do not yet fully understand how physiological processes and conditions such as interstitial flow or inflammation affect transport across interstitial tissue spaces and into lymphatics. This information is crucial to designing therapeutics that can target lymphatic vessels, and thus the downstream lymph nodes for immunotherapy. My lab’s research focuses on developing physiologically relevant in vitro model systems that can recapitulate conditions within peripheral tissues and designing nanoparticles to study biological barrier-nanoparticle interfaces to improve therapeutic outcomes, all with particular focus around lymphatic vessels and mucosal surfaces. We have determined that specific surface chemistry is required to maximize nanoparticle transport by lymph nodes, and that this transport is significantly modulated by physiological conditions such as interstitial flow. Furthermore, using nanoparticle probes, we have studied interstitial tissue spaces and found that there are spatial effects in interstitial tissue mesh spacing, particularly in the lymph nodes. We have also designed tunable systems to study mucosal barriers. Altogether our studies have provided new insights into regulation of lymphatic transport, new model systems for studying lymphatic transport, mucosal surfaces, and interstitial tissue spaces, and new design criteria to maximize targeting lymphatic transport for immunotherapy.