Matthew effect photoimmunotheranostics enabled by proton-driven nanoconverter

The construction of novel photothermal agents (PTAs) with near-infrared (NIR) light-responsive capacity that can differentiate normal and abnormal tissues bidirectionally to minimize adverse effects of photothermal therapy (PTT) is of great importance yet a huge challenge. We are developing “Matthew Effect Photoimmunotheranostics (MEP)”, demonstrated using an intelligent proton-driven enhanced nanoconverter (PEN) with self-refueling capacity by a facile polymerization method to form biocompatible photothermal agent polyaniline (PANI) with glucose oxidase (GOx) as the enhancer. PEN accumulates in the tumor region selectively after intravenous injection and GOx depletes glucose to re-establish the tumor microenvironment towards energy shortage and acidity aggravation, suppressing the expression of heat shock proteins to disturb the thermoresistance mechanism of tumor cells and promoting the proton-driven conversion of PANI to activated state synergistically. Strikingly, the PEN can differentiate normal and cancerous tissues bidirectionally with an “OFF-ON-OFF” mode to minimize adverse effects due to the enormous difference in glucose consumption between normal cells and tumor cells. PEN-mediated hyperthermia can induce immunogenic cell death. Under photoacoustic imaging and NIR-II light irradiation, PEN achieves tumor elimination with high specificity with synergistic mild hyperthermia/immune response by MEP. PEN-induced adaptive antitumor immunity is effective for eliminating distant tumors and suppressing tumor metastasis and recurrence.