Engineering a Photoactive Live Bacterial Hybrid: MXene/MoS2@M.bvs for Oxygenation-Boosted Cancer Immunotherapy

Abstract

Hypoxic conditions in the tumor microenvironment, which escape immune surveillance, are a major hindrance to controlling the antitumor effect of nanomaterials. In this work, MXene/MoS₂ @M.bvs photoactive live bacteria were developed. NIR irradiation elevates the oxygen level, induces the photothermal effect, interferes with the Ado A2A receptor (Adenosine A2AR) metabolic pathway, and triggers cancer immunotherapy. An acid-etched MXene sheet was fabricated from the MAX phase; exfoliated MoS₂ was composited with a thin MXene sheet to form self-assembled MXene/MoS₂. Nanocomposites were conjugated to Mycobacterium bovis (M.bvs) through a carbodiimide reaction, and they formed a stable rod shape, as confirmed through HRTEM analysis. The in vitro catalytic effect of MXene/MoS₂@M.bvs toward H₂O₂ was evaluated, and a reduction of the Ado level was observed by downregulation of A2AR expression. Nanocomposites not only improved the photothermal effect but also were directly involved in the immune stimulation. The level of cytokine production and cytotoxic T-cell activation was higher for MXene/MoS₂@M.bvs compared to the MXene/MoS₂. In vivo studies showed that MXene/MoS₂@M.bvs + NIR exhibited higher antitumor activity, longer survival time, biosafety, and inhibition of tumor growth. It also promotes DC maturation, increases TNF-α and IL-6, and induces a potent antitumor immune response. Overall, the photoactive live bacterial nanocomposites effectively enhance the synergistic effect of photothermal cancer immunotherapy.