Alexander Heiler

Bioengineering PhD Defense Presentation

November 18, 2025

3:30 PM

Location: IBB 1128 Suddath Room

Meeting link: https://gatech.zoom.us/j/8232545228?pwd=L0lSMHlBd2VtWXpqRHh0RHlOMmRnUT09&omn=95624185695

Advisor: Susan N. Thomas, Ph.D. (Woodruff School of Mechanical Engineering, Georgia Institute of Technology)

Committee Members:

M.G. Finn, Ph.D. (School of Chemistry and Biochemistry, Georgia Institute of Technology)

John Blazeck, Ph.D. (School of Chemical and Biomolecular Engineering, Georgia Institute of Technology)

Julie Champion, Ph.D. (School of Chemical and Biomolecular Engineering, Georgia Institute of Technology)

Jihoon Kim, Ph.D. (School of Integrative Engineering, Chung-Ang University)

Engineered nanoparticle surface chemistry potentiates lymph node-directed transport and synergistic immunotherapeutic co-delivery

To design more efficient treatments for complex diseases, the properties of drug delivery vehicles are often modulated to better overcome biological barriers and enhance the delivery of bioactive molecules to their intended target, such as immunotherapy delivery to the lymphatic system to mediate the immune response in diseases such as cancer, infection, or autoimmune disorders. This thesis develops nanomaterial platforms to enable controlled nanoparticle delivery across lymphatic barriers in support of combination immunotherapeutic delivery to modulate the immune response. To further elucidate design considerations for effective drug delivery systems for lymphatic disease immunomodulation and diagnosis, the surface properties of model poly(propylene sulfide) nanoparticles are engineered to modulate their lymphatic transport and control the co-conjugation of synergistic immunostimulatory molecules. The effects of the copolymer properties on the nanoparticle properties were explored, along with the transport behaviors of the nanoparticle formulations using in vitro assays modeling drainage into the lymphatic system that predicted their in vivo lymphatic transport, facilitating the rational design of lymphatic-targeting drug delivery vehicles with desired transport properties. Furthermore, the nanoparticle surface was functionalized to display two orthogonal reactive groups capable of co-conjugating distinct biomolecules in controlled ratios and stimuli-responsive cleavage. These capabilities were leveraged for the formation of a subunit nanovaccine, co-conjugating immunostimulatory adjuvant with varying extents of antigen to modulate the potency of the antigen-specific immune response. Beyond enabling the design of optimized vaccination platforms, the design approaches explored herein facilitate the formulation of general combination therapeutic delivery systems with controlled lymphatic-directed transport to advance multifaceted approaches to improve patient outcomes in complex diseases.