Enhancing the Anticancer Activity of Attenuated <i>Listeria monocytogenes</i> by Cell Wall Functionalization with “Clickable” Doxorubicin
Irene Lepori, Marta Roncetti, Marianna Vitiello, Elisabetta Barresi, Raffaella De Paolo, Paolo Maria Tentori, Caterina Baldanzi, Melissa Santi, Monica Evangelista, Giovanni Signore, Lorena Tedeschi, Claudia Gravekamp, Francesco Cardarelli, Sabrina Taliani, Federico Da Settimo, M. Sloan Siegrist, Laura Poliseno
Abstract
High Resolution Image Download MS PowerPoint Slide Among bacteria used as anticancer vaccines, attenuated Listeria monocytogenes (Lm at ) stands out, because it spreads from one infected cancer cell to the next, induces a strong adaptive immune response, and is suitable for repeated injection cycles. Here, we use click chemistry to functionalize the Lm at cell wall and turn the bacterium into an “intelligent carrier” of the chemotherapeutic drug doxorubicin. Doxorubicin-loaded Lm at retains most of its biological properties and, compared to the control fluorophore-functionalized bacteria, shows enhanced cytotoxicity against melanoma cells both in vitro and in a xenograft model in zebrafish. Our results show that drugs can be covalently loaded on the Lm at cell wall and pave the way to the development of new two-in-one therapeutic approaches combining immunotherapy with chemotherapy.