Targeting Melanoma Hypoxia with the Food-Grade Lactic Acid Bacterium <i>Lactococcus Lactis</i>

• Main Authors: Rodolfo Garza-Morales, Beatriz E. Rendon, Mohammad Tariq Malik, Jeannete E. Garza-Cabrales, Anne Aucouturier, Luis G. Bermúdez-Humarán, Kelly M. McMasters, Lacey R. McNally, Jorge G. Gomez-Gutierrez
• Format: Article
• Language: English
• Published: MDPI AG 2020-02-01
• Series: Cancers
• Subjects: <i>lactococcus lactis</i>; probiotic; hypoxia; melanoma; tumor microenvironment; msot; advance molecular imaging (ami), targeted therapies; solid tumors
• Online Access: https://www.mdpi.com/2072-6694/12/2/438

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. <i>Lactococcus lactis</i> 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 <i>L. lactis</i> can target and localize within melanoma hypoxic niches. To simulate hypoxic conditions <i>in vitro</i>, melanoma cells A2058, A375 and MeWo were cultured in a chamber with a gas mixture of 5% CO₂, 94% N₂ and 1% O₂. Among the cell lines tested, MeWo cells displayed greater survival rates when compared to A2058 and A375 cells. Co-cultures of <i>L. lactis</i> expressing GFP or mCherry and MeWo cells revealed that <i>L. lactis</i> 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 <i>L. lactis</i> expressing &#946;-galactosidase (&#946;-gal) or infrared fluorescent protein (IRFP713) results in the establishment of the recombinant bacteria within tumor hypoxic niches. Overall, our data suggest that <i>L. lactis</i> represents an alternative strategy to target and deliver therapeutic molecules into the tumor hypoxic microenvironment.