Researcher(s)
- Harsh Desai, Biomedical Engineering, University of Delaware
Faculty Mentor(s)
- Jason Gleghorn, Biomedical Engineering, University of Delaware
Abstract
Lymph nodes (LNs) are critical immunological organs responsible for coordinating adaptive immune responses. Their specialized architecture ensures that immune cells efficiently recognize and respond to foreign antigens. However, this same structure presents challenges for drug delivery. Lobules within the LN, where immune activation occurs, are highly isolated. Entry is regulated by high endothelial venules (HEVs), which restrict most small molecules and non-targeted therapeutics. As a result, conventional drug delivery methods fail to efficiently reach LN compartments, limiting therapeutic outcomes in diseases like metastatic cancer. To overcome this, our lab developed T-lymphocyte-derived therapeutic vehicles that mimic the natural LN-homing ability of T cells. These carriers have demonstrated a >700% increase in small molecule delivery to LNs, and ongoing work in the group seeks to expand delivery efficiency and tunability. This project explores both manufacturing optimization and development of an in vitro evaluation platform to further advance the drug delivery technology. As part of manufacturing, cell-derived materials must be precisely isolated. A sample preparation protocol was developed to maximize yield and purity while preserving function. Batches were assessed for consistency against full cell preparations, with quality evaluated via lipid/protein assays, morphology, and functional tests. Standardizing this process is essential for improving manufacturing consistency, enhancing drug-loading capacity, and ensuring biological function of the carriers. Next, a dendritic cell model was produced from a human monocyte line, THP-1, via cytokine and signaling molecule treatments. Microscopy and a custom image analysis pipeline were used to evaluate morphometry to determine successful differentiation. This in vitro model will ultimately be used to evaluate payload functionality for LN-dendritic cell targeted therapies. Coupled together, this work will support the broader goal of delivering more effective, targeted therapeutics for LN-resident diseases.