Work

Material‐Encoded Synchronization of Immunogenic Cell Death With Adenosine A2A Receptor Blockade Reprograms the Tumor Microenvironment

Year: 2026

Type: article

Abstract: Adenosine rapidly suppresses antitumor immunity through the adenosine A2A receptor (A2AR). Immunogenic cell death (ICD) releases extracellular ATP, which can be rapidly converted into immunosuppressive adenosine. We therefore designed BSCS@PHY to synchronize ICD induction with local A2AR blockade in the same spatiotemporal window, aiming to protect antigen priming from adenosine-mediated suppression. BSCS@PHY integrates a bismuth-copper diselenide core for photothermal heating, glutathione depletion, and chemodynamic hydroxyl-radical generation; hyaluronic-acid-modified phase-change materials for on-site activation; the A2AR antagonist SCH442416 for local A2AR blockade; and yeast cell wall (YCW) components for innate adjuvanticity. Thermography-guided irradiation confines activation within a controlled window, melts the phase-change shell to expose the catalytic surface, and coordinates ICD amplification with co-localized A2AR blockade and dendritic-cell activation. In 4T1 tumors, BSCS@PHY enables image-guided activation, enhances ICD hallmarks, lowers adenosine signaling, promotes dendritic-cell maturation and T-cell priming, and improves tumor control, with additional benefit when combined with anti-PD-L1. Loss-of-function comparisons support nonredundant contributions of A2AR blockade and YCW-mediated adjuvanticity. This material-encoded strategy aligns danger-signal generation with local A2AR blockade in the same tumor niche and offers a framework for pairing ICD induction with metabolic-checkpoint control in cold tumors.

Source: Advanced Science

DOI: 10.1002/advs.76303