Assessing the Effect of Liposomal Spherical Nucleic Acid stability on Vaccine Function for Triple Negative Breast Cancer

Jun 30, 2020 | NURJ x EXPO 2020 Presentation

Leah Broger

Adviser: Chad Mirkin
Subject: Neuroscience
DOI: 10.21985/n2-zyw0-4f51

Over the course of her undergraduate career, Leah developed a deep-seated fascination with the biological interactions that govern higher order physiological phenomena. After attending Dr. Chad Mirkin’s guest lecture on nanomaterials her freshman year, Leah became specifically interested in the novel properties of nanostructures and their propitious biomedical applications. Leah’s curiosity ushered her into her first research experience at a Dutch biotech startup. Here, Leah optimized bacterial extraction for a diagnostic device, by testing capture efficiencies of gold magnetic nanobeads on patient samples. Presently, in Dr. Chad Mirkin’s Lab, Leah is investigating the stability and effects of liposome composition in liposomal spherical nucleic acids (SNA), to increase efficiency of targeted cargo release in triple-negative breast cancers. This past year, Leah was awarded Northwestern’s selective Academic Year Grant to further probe the chemical and structural basis for oxidation-enhanced immunogenicity, as well as the effects of SNA structure and stability on vaccine function. Leah graduated in Spring 2020 with a bachelor’s degree in Neuroscience, Biochemical Engineering, and Biotechnology.

Abstract

The successful development of vaccines for triple negative breast cancer (TNBC) has been hindered because there are no identified tumor-associated antigens. As an alternative to peptide vaccines, the administration of tumor lysates has been investigated in TNBC to activate the immune system against tumors, wherein a mixture of tumor-specific lysates is administered to behave as antigens. The Mirkin group has previously demonstrated the capability of Liposomal Spherical Nucleic Acids (SNAs) to initiate antigen presentation and activate immune cells. Liposome SNA’s consist of a concentric phospholipid vesicle core where the adjuvant is anchored into the bilayer, and the lysate is encapsulated within the core. With this novel delivery method in mind, we proposed a two-pronged investigation. First, we assessed whether changing the stability of the SNA impacts antigen delivery, by comparing four different lipid constituents and their decay rate in serum. Second, we investigated whether changing the hydrophobicity of the DNA anchor affected SNA decay rate. From these investigations, we find that SNA stability is governed by both liposome membrane fluidity and anchor hydrophobicity, and that these parameters are additive. Taken together, our findings will be able to significantly optimize the way cancer vaccines for TNBC are designed and administered.