Researcher(s)
- Katherine Zucaro, Biomedical Engineering, University of Delaware
Faculty Mentor(s)
- Jason Gleghorn, Biomedical Engineering, University of Delaware
- Ryan Zurakowski, Biomedical Engineering, University of Delaware
Abstract
Transport into the lymph node (LN) lobule, where metastasis occurs, is highly regulated and often excludes therapeutics, leaving the metastasis untreated by chemotherapy. Utilizing a “Trojan horse” strategy, our group has engineered an innovative cell-mimetic drug carrier: cryo-shocked T-lymphocytes (CSTLs). This approach leverages cellular properties to target and efficiently deliver small-molecule chemotherapeutics to the LN lobule. However, CSTLs have suboptimal release kinetics. Therefore, we aimed to further engineer the CSTLs to provide delayed, sustained release by incorporating a hydrogelated core, termed intracellular hydrogelated T-lymphocytes (HTCs). We hypothesized that encapsulation of small molecule drugs inside the hydrogel core would enable a significant change to the release kinetics. In this study, we compared the drug release profiles of loaded HTCs to those of CSTLs to evaluate their potential for sustained drug delivery. CSTLs and HTCs were both loaded with anti-cancer drug doxorubicin (DOX). To test release, samples were resuspended in 0.9% NaCl (saline), placed in the apical chamber of a transwell insert with fresh saline in the basal chamber and placed on a rocker at 37°C. Basal chamber was periodically sampled and assessed via plate reader, where the absorbance of DOX was measured at 480 nm. The average of three samples was used to calculate the amount of DOX released using a DOX standard curve. Cumulative release curves for CSTLs and HTCs were generated. On comparison, we found that incorporating a hydrogel into our carrier system significantly slows the release of DOX. These data reveal that HTCs have a slower drug release rate than CTSLs making them a suitable option for sustained drug delivery.