Self-Propelled and Near-Infrared-Phototaxic Photosynthetic Bacteria as Photothermal Agents for Hypoxia-Targeted Cancer Therapy

Hypoxia can increase the resistance of tumor cells to radiotherapy and chemotherapy. However, the dense extracellular matrix, high interstitial fluid pressure, and irregular blood supply often serve as physical barriers to inhibit penetration of drugs or nanodrugs across tumor blood microvessels into hypoxic regions. Therefore, it is of great significance and highly desirable to improve the efficiency of hypoxia-targeted therapy. In this work, living photosynthetic bacteria (PSB) are utilized as hypoxia-targeted carriers for hypoxic tumor therapy due to their near-infrared (NIR) chemotaxis and their physiological characteristics as facultative aerobes. More interestingly, we discovered that PSB can serve as a kind of photothermal agent to generate heat through nonradiative relaxation pathways due to their strong photoabsorption in the NIR region. Therefore, PSB integrate the properties of hypoxia targeting and photothermal therapeutic agents in an "all-in-one" manner, and no postmodification is needed to achieve hypoxia-targeted cancer therapy. Moreover, as natural bacteria, noncytotoxic PSB were found to enhance immune response that induced the infiltration of cytotoxicity T lymphocyte. Our results indicate PSB specifically accumulate in hypoxic tumor regions, and they show a high efficiency in the elimination of cancer cells. This proof of concept may provide a smart therapeutic system in the field of hypoxia-targeted photothermal therapeutic platforms.