The majority of high-grade serous ovarian cancer (HGSOC) patients are diagnosed at late stages in disease progression (stage III/IV), which leads to extremely low cure rates with current surgical and chemotherapy interventions. Further, of the meager surviving patient population, over 80% will experience relapse due to the persistence of a small, clinically undetectable population of chemotherapy-resistant cancer cells known as minimal residual disease (MRD), and in this event, the disease is considered incurable. In many other types of cancer, chemoresistance has been overcome with the introduction of immunotherapies, but HGSOC has yet to see the impact of these emerging therapies as their tumor environment is considered “cold” with limited immune cell infiltration. However, recent work has shown the potential of type I interferon as a means to recruit immune cells to HGSOC tumor sites, allowing these cells to then target and eliminate the cancer cells. In the case of MRD, the delivery of type I interferon is limited by the cytokine’s high toxicity and poor pharmacokinetics while attempting to target such a small cell population.
Thus, in this work, we engineer layer-by-layer nanoparticles (LbL NPs) for the targeted delivery of immunotherapies to ovarian cancer at the MRD stage. In particular, we focus on optimizing the expression, purification, and conjugation of the cytokine interferon-α (IFN-α) for this NP system. Once tethered to a liposome core, the IFN- α-conjugated NP is then layered with a polymeric coating that yields potent HGSOC-specific delivery. This polymeric LbL NP is thoroughly characterized and evaluated for its ability to colocalize with ovarian cancer cells as well as induce an inflammatory response in the HGSOC tumor microenvironment. In all, this LbL NP platform provides a novel approach to targeting cancer cells at the MRD stage as promising strategy for improving the efficacy of immunotherapies in HGSOC.
