A bacteria-releasing mucoadhesive sheet for localized delivery and penetrative therapy of gastrointestinal cancer

Abstract

Bacteria-based cancer therapy shows promise for solid tumors, but effective localization and long-term retention in the gastrointestinal (GI) tract remain limited by peristalsis and fluid flow. We developed a Bacteria-Releasing Mucoadhesive Sheet (BRMS), a deployable multilayered platform for precise localized, active bacterial delivery. The BRMS consists of three functional layers: an unrolling layer for rapid deployment and conformal adhesion to the mucosa; a guard layer to minimize bacterial loss and enforce unidirectional release; and a therapeutic layer loaded with engineered Salmonella secreting the anticancer protein VC1. In its rolled state, the BRMS is compatible with delivery via standard endoscopes or capsule robots. Upon deployment, it protects bacteria from the luminal environment, prolongs local retention, and promotes penetration into deep tumor tissue. We validated its spatiotemporally controlled delivery and deployment through ex vivo experiments. In a CT-26 colon cancer mouse model, the BRMS achieved robust tumor growth inhibition and regression without detectable systemic toxicity. In conclusion, the BRMS is a novel bacterial delivery platform that overcomes GI physiological barriers, enabling sustained bacterial infiltration into deep tumor regions, and offering a powerful strategy to extend the therapeutic potential of bacteria-based cancer therapies.