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Drug Delivery

Drug Delivery - Poster Session C

Poster W18 - Iron-tannin coating reduces clearance and increases tumor colonization of systemically delivered bacteria

Friday, October 25, 2024
10:00 AM – 11:00 AM EST
Location: Exhibit Hall E, F & G

Introduction: Engineered bacteria offer a novel approach to targeted cancer therapy, but challenges remain in delivering enough bacteria safely for effective treatment. Previous efforts have used either a native or synthetic coating to achieve better control over the half-life of bacteria in the body, but have limitations in delivery or versatility. Using a simple one-pot chemical process, we coated bacteria with iron and tannic acid to form a temporary adhesive, protective coating surrounding the bacterial cell surface.

Materials and

Methods: In this work, we optimized and evaluated a synthetic coating for probiotic Escherichia coli Nissle 1917 to increase half-life with intravenous delivery and thereby increase bioavailability of low doses of bacteria to colonize and treat tumors. The ratio of reagents was optimized to reduce the coating's occlusion risk in intravenous settings. Then the coating was characterized in terms of adhesion, protection of bacteria in blood, and in vivo.

Results, Conclusions, and Discussions: The optimized iron and tannic acid (FeTA) coated bacteria of several different genetic backgrounds showed up to 15-fold higher survival in blood survival assay for up to four hours. We found that the iron and tannic acid coating reduced both complement-mediated bacterial killing and phagocyte-mediated bacterial killing in vitro. The resulting increased circulation time after systemic delivery of attenuated bacteria allowed for up to 50% colonization efficiency of iron and tannic acid coated bacteria in a subcutaneous lymphoma mouse tumor model compared to 0% for the non-coated control. Altogether, we show that an optimized FeTA coating significantly extends the half-life and colonization efficiency of engineered bacteria, overcoming a key limitation to their application in cancer therapy.

Acknowledgements (Optional):