Mathematical Modeling of Bacteria-Enabled Drug Delivery System Penetration into Multicellular Tumor Spheroids

Bacteria-based cancer treatment is a promising approach to address the need for targeted tumor therapies in an effort to avoid the systemic toxicity inherent in conventional chemotherapy. A number of bacterial strains have been shown to preferentially colonize tumors and impart therapeutic benefits. However, the physical underpinnings of bacteria intratumoral transport remain poorly studied. It is hypothesized that cell Iysis in hypoxic and necrotic regions of tumors creates a niche in which some bacteria thrive. To understand if preferential growth plausibly explains the experimentally observed bacterial colonization profiles, we have developed a mathematical model incorporating transport and growth dependent on tumor cell Iysate. We fit model parameters to experimental data, showing that our formulation captures experimentally observed trends. Moreover, we find that bacteria have a higher effective diffusivity than nanoparticles alone, demonstrating transport advantages to designing bacteria-based cancer therapy. This model serves as a first step towards building computational tools for designing optimized bacteria- based chemotherapeutic delivery systems.