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.