Diffusion-Controlled Therapeutic Delivery via Engineered Bacterial Biofilm Scaffolds in Oncology

Bacteria-based cancer therapies have re-emerged as a promising modality due to the intrinsic capacity of certain bacterial species to preferentially colonize hypoxic and necrotic tumor regions [1, 2]. However, planktonic motile systems are frequently limited by rapid immune clearance, transient persistence, and uncontrolled payload release [2, 3]. This review introduces a synthetic biology framework that reframes bacterial biofilms from pathological barriers into programmable therapeutic scaffolds. By utilizing programmable microbial therapeutic chassis, researchers can enhance therapeutic duration within the tumor microenvironment (TME) while potentially minimizing systemic exposure [4, 5]. Central to this framework is the genetic modulation of matrix density, primarily via curli fiber-associated csgA expression. This approach may enable drug release kinetics governed by Fickian diffusion principles, allowing for sustained and controllable therapeutic delivery [6, 7].