Mimicking nature with nanotechnology: engineering gold nanoparticles for targeted protein interactions
Wo, Anita
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Permalink
https://hdl.handle.net/2142/130035
Description
Title
Mimicking nature with nanotechnology: engineering gold nanoparticles for targeted protein interactions
Author(s)
Wo, Anita
Issue Date
2025-07-15
Director of Research (if dissertation) or Advisor (if thesis)
Murphy, Catherine J
Doctoral Committee Chair(s)
Murphy, Catherine J
Committee Member(s)
Gruebele, Martin
Chan, Jefferson
Leal, Cecilia
Department of Study
Chemistry
Discipline
Chemistry
Degree Granting Institution
University of Illinois Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Gold nanoparticles
nano-bio interactions
fibrinogen
Abstract
Colloidal nanoparticles show great versatility in biological applications, which include diagnostics, therapeutics, targeted drug delivery, biosensing, and bioimaging. Gold nanoparticles (AuNP) are particularly attractive materials due to several desirable properties including: 1) biocompatibility due to their physiologically inert nature, 2) size tunability within the range of 1-100nm, and 3) easy modification of surface chemistry composition. Control over the customizable properties of nanoparticle design allows for greater selectivity in its application. As the applications of nanoparticles are becoming increasingly integrated into healthcare, further research into the interactions of nanoparticles within complex living systems is required. Chapter 1 introduces the biomedical potential of nanoparticles and emphasizes the importance of understanding and predicting their behavior in biological environments. A central challenge in the field is that nanoparticles acquire a biological identity upon exposure to biological fluids due to biomolecular adsorption, which can lead to undesirable outcomes. Major translational barriers include biocompatibility, immune activation, and off-target effects, and reviews strategies for surface engineering to mitigate these issues. Fibrinogen, an abundant blood protein, was selected as a protein of interest to investigate the influence of nanoparticle surface design on protein binding behavior. In Chapter 2, a synthetic platform was developed in which dithiol peptides were grafted onto the surface of spherical AuNPs to mimic protein–ligand interactions. By tuning peptide density, it was possible to control conformational display on the nanoparticle surface, enabling selective binding to Mac-1 (αMβ2 integrin), a fibrinogen-binding receptor. The nanoparticles demonstrated strong binding affinity and specificity to Mac-1 at both the molecular and cellular levels, even outperforming native fibrinogen in some cases. Chapter 3 builds on these findings by introducing additional conformational constraint using cyclic peptides. A systematic library of cyclic peptide–AuNP conjugates was synthesized with spatial tuning. These constructs showed improved binding to Mac-1 at the molecular level, though further optimization is needed to translate similar binding outcomes at the cellular level. Together, this work provides a deeper understanding of how introducing peptide conformation on nanoparticle surfaces can result in protein mimics capable of targeted protein interactions.
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