Microbial β-Glucuronidase Hydrogel Beads Activate Chemotherapeutic Prodrug

Bacteria-assisted chemotherapeutics have been highlighted as an alternative or supplementary approach to treating cancer. However, dynamic cancer–microbe studies at the in vitro level have remained a challenge to show the impact and effectiveness of microbial therapeutics due to the lack of relevant coculture models. Here, we demonstrate a hydrogel-based compartmentalized system for prodrug activation of a natural ingredient of licorice root, glycyrrhizin, by microbial β-glucuronidase (GUS). Hydrogel containment with Lactococcus lactis provides a favorable niche to encode GUS enzymes with excellent permeability and can serve as an independent ecosystem in the transformation of pro-apoptotic materials. Based on the confinement system of GUS expressing microbes, we quantitatively evaluated chemotherapeutic effects enhanced by microbial GUS enzyme in two dynamic coculture models in vitro (i.e., 2D monolayered cancer cells and 3D tumor spheroids). Our findings support the processes of prodrug conversion mediated by bacterial GUS enzyme which can enhance the therapeutic efficacy of a chemotherapy drug under dynamic coculture conditions. We expect our in vitro coculture platforms can be used for the evaluation of pharmacological properties and biological activity of xenobiotics as well as the potential impact of microbes on cancer therapeutics.