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 Photo-immunotheranostics (MEP)", demonstrated using an intelligent proton-driven enhanced nanoconverter (PEN) with self-refueling capacity by a facile polymerization method to form biocompatible photothermal agent pol-yaniline (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 thermore-sistance mechanism of tumor cells and promoting the proton-driven conversion of PANI to activated state syn-ergistically. 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.