Biomimetic Nanoparticles for the Homotypic Targeting of Triple-Negative Breast Cancer

• Grace Azevedo, Chemical Engineering, University of Delaware

• Emily Day, Biomedical Engineering, University of Delaware

Triple negative breast cancer (TNBC) accounts for 15-20% of all breast cancer diagnoses, and is characterized by its lack of expression of estrogen (ER), progesterone (PR), and human epidermal growth factor receptor 2 (HER2) receptors, the three most common cell membrane receptors present on other subtypes of breast cancer. This lack of receptor expression hinders the development of effective targeted treatments for TNBC, resulting in higher recurrence and mortality rates among TNBC patients. Currently, the only available treatment options for TNBC patients are surgery, radiotherapy, chemotherapy, or a combination of two or more of these treatments, all of which have adverse side effects and lack the ability to specifically target the tumor without damaging healthy tissues. Therefore, there is an urgent clinical need to develop effective treatments that can target the tumor and improve patient outcomes. Recent studies suggest that coating nanoparticles (NPs) with cancer cell-derived membranes can improve their tumor delivery via homotypic targeting. Homotypic targeting is thought to be achieved by the the presence of special cell membrane proteins and adhesion molecules that include “markers of self” proteins that hide the NPs from the immune system, prolonging their circulation time in the blood and thus increasing their chances of accumulating at the tumor, as well as “self-recognition” proteins that enable cancer cell-specific binding of the NPs. Thus, we wrapped light-sensitive gold nanoshells (NS) with 4T1 TNBC murine cell membranes, forming 4T1-NS to enable the NS to target the tumor via homotypic targeting. Here, we present results of in vitro studies confirming the successful synthesis and characterization of cancer cell membrane-wrapped gold  nanoshells that demonstrate greater targeting and uptake in TNBC cells over non-cancerous breast epithelial cells. We also investigate the expression of TNBC cell membrane adhesion molecules via immunocytochemistry to better understand homotypic targeting. This work provides a promising biomimetic platform to improve the targeting and delivery of nanoparticles to TNBC for improved treatment outcomes.