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

Area of Science:

• Oncology
• Microbiology
• Biomedical Engineering

Background:

• Bacteria-based cancer treatment offers targeted therapy with reduced systemic toxicity compared to chemotherapy.
• Bacterial colonization of tumors is observed, but the mechanisms of intratumoral transport are not well understood.
• Tumor microenvironments, including hypoxic and necrotic regions, may create niches favoring bacterial survival and growth.

Purpose of the Study:

• To investigate the physical underpinnings of bacteria's intratumoral transport.
• To develop a mathematical model explaining bacterial colonization profiles based on transport and growth.
• To assess the transport advantages of bacteria over nanoparticles for cancer therapy.

Main Methods:

• Development of a mathematical model incorporating bacterial transport and growth dependent on tumor cell lysate.
• Fitting model parameters to experimental data to validate the model's predictive capabilities.
• Comparison of effective diffusivity between bacteria and nanoparticles within the tumor microenvironment.

Main Results:

• The mathematical model successfully captured experimentally observed bacterial colonization trends.
• Bacteria demonstrated a higher effective diffusivity than nanoparticles alone.
• The findings support the hypothesis that bacterial growth in tumor-derived niches contributes to colonization patterns.

Conclusions:

• Mathematical modeling provides insights into bacteria-based cancer therapy mechanisms.
• Bacteria possess inherent transport advantages for intratumoral drug delivery.
• This work lays the foundation for computational tools to optimize bacteria-based cancer treatment strategies.