Abstract
Despite current advancements in cancer therapeutics, ovarian cancer treatments remain insufficient, with five-year survival rates around 50% (Chan et al., 2006). Known as the “silent killer,” ovarian cancer is one of the most lethal gynecological malignancies due to delayed diagnoses from nonspecific symptoms and limited screening. By the time symptoms emerge, the disease has progressed to advanced stages involving peritoneal metastases, where cancer spreads to the abdominal cavity. These metastases complicate treatment, reduce long-term survival, and significantly increase the recurrence rate. Current treatments – cytoreductive surgery to remove visible tumor masses, followed by intraperitoneal chemotherapy to eliminate microscopic residual cancer cells – rely on nonspecific cytotoxicity in high drug concentrations. This not only damages healthy tissues but also fails to fully prevent recurrence due to remaining residual intra-abdominal lesions. Hence, there is an urgent clinical need to develop more precise, tumor-specific therapeutic strategies that can be accessible to patients, taking into consideration the social responsibility to mitigate systemic inequities in healthcare systems.
Liposomes – small vesicles composed of phospholipid bilayers – provide a versatile platform for targeted drug delivery. They allow for encapsulation and subsequent delivery of both imaging agents and biologically active drugs, enabling simultaneous treatment and monitoring. With this, my Capstone project aims to develop tumor-targeted liposomes containing alpha radioactive isotopes. Concurrently, we aim to engineer a reproducible manufacturing process for efficient clinical translation. Alpha isotopes emit high-energy particles with short path lengths, making them ideal for localized eradication of small clusters of cancer cells while minimizing collateral damage to surrounding healthy tissue. These isotopes are delivered via liposomes functionalized to selectively bind mannose receptors, which are overexpressed in tumor microenvironments. To enhance liposome uniformity and scalability, we use a microfluidic hydrodynamic focusing (MHF) system, which controls particle size and composition, ensuring stable biodistribution and safety for clinical applications. With a proper MHF system, these radiotheranostic therapies can be mass produced with high precision, thus reducing the financial burden that is associated with ovarian cancer peritoneal metastases treatment. Over the course of our project, we standardized liposome formulations and microfluidic parameters for optimal size (100-150 nm) and polydispersity (PDI < 0.3), enabling scalability and reproducibility with ease. We have also established tumor specificity of functionalized liposomes as a proof of concept, concurrently ensuring minimal off-target toxicity. Our next step is testing in murine models using comparative PET/CT imaging to assess liposome localization and therapeutic efficacy.
While such technical innovations hold transformative potential, access to care is not evenly distributed. Socioeconomic status (SES), geographic location, race, and insurance coverage all play critical roles in determining cancer outcomes, particularly in ovarian cancer. Early detection and timely treatment are strongly correlated with access to preventive healthcare, which is more readily available to higher-income, insured, and urban populations. In contrast, women from rural regions or with lower SES are at higher risk for mortality. My aim for my STS research was to understand the interdependency of innovation and healthcare disparities in order to bridge the existing gap so that patients can receive the necessary treatments. Through my research, I found a correlation between SES and ovarian cancer outcomes, with those of lower SES being 15% less likely to receive treatment compared to their higher SES counterparts (Karanth et al., 2019). Furthermore, women with lower SES are more likely to live in geographically isolated or lower-income regions, which consequently have fewer clinics and gynecological oncologists (Graham et al., 2019). Intertwined with these are race and insurance coverage, with uninsured and Black women are more likely to be diagnosed at late stages and thus experience higher mortality rates (Mei et al., 2023). Additionally, minority women experience more hesitancy to receive care due to past discrimination or a lack of knowledge to navigate complex healthcare systems. As new technologies emerge, advanced treatments may remain concentrated in well-funded institutions, creating a two-tiered system in which only certain populations benefit. Therefore, it is essential for researchers to consider the accessibility and cost-efficacy early in the innovation process to ensure equitable access.
The synthesis of my technical and STS research highlights the intersectionality between biomedical innovation with the societal dimensions of healthcare. While targeted liposomal therapies represent a significant advancement in ovarian cancer treatment, their impact ultimately depends on who can access them. Scientific progress does not occur in isolation; it interacts with broader social systems that shape who benefits from them and who is ultimately left behind. Only by coalescing ethical evaluation with technical progress can there exist a solution that addresses both the physical disease and invisible disease of inequities within the health sector.
