Targeting Melanoma Hypoxia with the Food-Grade Lactic Acid Bacterium

Melanoma is the most aggressive form of skin cancer. Hypoxia is a feature of the tumor microenvironment that reduces efficacy of immuno- and chemotherapies, resulting in poor clinical outcomes. is a facultative anaerobic gram-positive lactic acid bacterium (LAB) that is Generally Recognized as Safe (GRAS). Recently, the use of LAB as a delivery vehicle has emerged as an alternative strategy to deliver therapeutic molecules; therefore, we investigated whether can target and localize within melanoma hypoxic niches. To simulate hypoxic conditions , melanoma cells A2058, A375 and MeWo were cultured in a chamber with a gas mixture of 5% CO, 94% N and 1% O. Among the cell lines tested, MeWo cells displayed greater survival rates when compared to A2058 and A375 cells. Co-cultures of expressing GFP or mCherry and MeWo cells revealed that efficiently express the transgenes under hypoxic conditions. Moreover, multispectral optoacoustic tomography (MSOT), and near infrared (NIR) imaging of tumor-bearing BALB/c mice revealed that the intravenous injection of either expressing β-galactosidase (β-gal) or infrared fluorescent protein (IRFP713) results in the establishment of the recombinant bacteria within tumor hypoxic niches. Overall, our data suggest that represents an alternative strategy to target and deliver therapeutic molecules into the tumor hypoxic microenvironment.