Integrating Bacteria with a Ternary Combination of Photosensitizers for Monochromatic Irradiation-Mediated Photoacoustic Imaging-Guided Synergistic Photothermal Therapy

Photosensitizer-based therapy often suffers from unitary and easily attenuated photosensitive effects, limited tumor penetration and retention, and requirement of multiple irradiation for combination therapy, which largely restrict its application. Here, bacteria are integrated with a monochromatic irradiation-mediated ternary combination of photosensitizers for photoacoustic imaging-guided synergistic photothermal therapy. Bacteria that are bioengineered to express natural melanin are decorated with dual synthetic photosensitizers by nanodeposition with indocyanine green and polydopamine under a cytocompatible condition. The combined photosensitizers, which share an adequate excitation at 808 nm, endow integrated bacteria with a stable triple photoacoustic and photothermal effect under a monochromatic irradiation. Due to their living characteristics, these bacteria preferentially colonize hypoxic tumor tissue with homogeneous distribution and durable retention and generate uniform imaging signals and a sufficient heating of tumor upon laser irradiation. Supported by significantly inhibited tumor growth and extended survival of animals in different tumor-bearing murine models, our work proposes the development of bacteria-based innovative photosensitizers for imaging-guided therapy.