Nanoscale surface engineering for bioimaging and drug delivery

Abstract

BIOMEDICAL ENGINEERING

NANOSCALE SURFACE ENGINEERING FOR BIOIMAGING AND DRUG DELIVERY

ASHWATH JAYAGOPAL

Dissertation under the direction of Professor Frederick R. Haselton

Nanoengineering of device interfaces permits the presentation of information at length scales consistent with biological processes. This dissertation describes three distinct nanoscale surface engineering strategies with the aim of expanding the scope of applications of nanotechnology in bioimaging and drug delivery. Specifically, the surface engineering approaches utilized in this work are focused on the enhancement of nanoscale device targeting and the development of multifunctional devices. The first aim of this work was focused on the surface functionalization of quantum dot nanocrystals with chemically-modified antibodies or cell penetrating peptides to enable in vivo multiplexed cellular and biomolecular detection applications in vascular disease. Nonspecific quantum dot-antibody binding to endothelial cell surfaces was markedly reduced using an Fc fragment blockade technique, which enabled the simultaneous detection of up to four cellular and/or molecular mediators of diabetes and uveitis. Functionalization of quantum dots with peptides enabled the long-term tracking of leukocyte subset recruitment to atherosclerotic plaques in animal models. In the second aim, nanoscale imaging agents and therapeutics were simultaneously packaged within a lipid matrix for multimodal applications, and translocation mechanisms of surface-functionalized, multimodal lipid nanoparticles across cellular barriers were investigated. Surface engineering of lipid nanoparticles with an anionic polymer coating enabled the translocation of the carrier across cell membranes in vitro. Functionalization of nanoparticles with a trifunctional coating promoted the transcellular transport of lipid nanoparticles across endothelial cell barriers in vitro. Nanoscale payloads incorporated into lipid matrices included quantum dots, iron oxide nanoparticles, gold colloids, and the chemotherapeutic agent paclitaxel. The multimodality of lipid nanoparticles was demonstrated by the optical and magnetic resonance imaging of 4T1 mammary carcinoma cells loaded with lipid nanoparticles featuring iron oxide nanoparticles and quantum dots.