Release Kinetics of SN38 Loaded NPs

• Aurora Van Auken, Biomedical Engineering, University of Delaware

• Emily Day, Biomedical Engineering, University of Delaware

Triple-Negative Breast Cancer (TNBC) is a subtype that makes up for roughly 20% of all breast cancer diagnoses and lacks 3 receptors used for traditional hormonal and targeted therapies causing a 5-year survival rate ranging from 12-65%. However, Trop2 is an overexpressed cellular receptor in TNBC and has been targeted by an antibody-drug conjugate (ADC), Trodelvy. Trodelvy delivers SN38, a cytotoxic drug which depends on a carrier to be delivered to tumor cells. Trodelvy shows promise for the use of SN38 when treating TNBC but has side effects making it unideal. Previous research supports the use of poly (lactic-co-glycolic acid) PLGA nanoparticles (NPs) to encapsulate and deliver chemotherapeutic drugs. Further engineering these NPs utilizing cancer cell membranes (MWNPs) and anti-body conjugation (AbNPs) improves homotypic targeting and targeting efficiency, respectively. Bare NPs exhibit accumulation of drug in healthy tissue due to the lack of targeting, while MWNPs have exhibited limited drug release in healthy tissue and increased accumulation within tumors. Similarly, AbNPs have shown increased targeting to tumor sites. AbNPs and MWNPs should be compared to investigate chemotherapeutic effects. With this, release kinetics studies will be used to analyze how much cargo is encapsulated in the nanocarriers after a period of time. These studies will be useful in clinical applications to understand how much drug is being released into the body/tumor after treatment. Idealistically, the cargo should be released and degraded within the tumor microenvironment (TME) which houses an acidic environment (pH 5) in comparison to the blood stream (pH 7). Bare NPs, AbNPs, and MWNPs groups will be assessed over the span 72 hours in 5% BSA in pH 7 and pH 5 to mimic the physiological conditions of the blood stream and the TME, respectively.