Prca-09 Treatment of Triple Negative Breast Cancer Brain Metastases via Multi-Agent Poly(2-Oxazoline) Micelles

Abstract As the largest contributor to cancer-related mortality in women, breast cancer is responsible for approximately 685,000 global deaths per year. However, due to recent technological advances, breast cancer survival lengths have extended, which has coincided with a higher occurrence of late-stage breast cancer. At this stage of disease progression, metastasis to the brain, lungs, bone, and liver is common and drastically escalates the lethality of the disease. Brain metastases (BMs) are especially devastating on account of the resulting neurological deficits and limited treatment options; this is primarily due to the brain’s intricate microenvironment and the difficulty in overcoming the blood-brain barrier (BBB). Current clinical treatment strategies either require invasive approaches to bypass the BBB or rely on chemotherapy and radiation to slightly prolong survival. Thus, an effective non-invasive therapy that delivers therapeutics across the BBB is a highly sought yet elusive solution. Our platform poly(2-oxazoline) micelles demonstrate improved delivery and therapeutic success to brain tumors through increased circulation. In addition to increasing circulation, these micelles enhance drug solubility, have high drug loading, and can encapsulate multiple therapeutics within a singular micelle. Previously, rationally designed formulations successfully delivered chemo- and immunotherapeutics for the synergistic treatment of primary triple negative breast cancer (TNBC). Due to this strategy’s success and the platform’s improvement of brain delivery, we hypothesize that a combination of chemotherapeutic and immunotherapeutic agents in poly(2-oxazoline) micelles will improve outcomes for patients with TNBC BMs. Our initial efforts involve formulating chemo-immunotherapeutic encapsulating polymeric micelles and evaluating them in an immunocompetent animal model. Overall, this work aims to create a non-invasive therapy for TNBC BMs that extends survival time and mitigates symptoms.