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.

Automated summary

This study develops an intelligent proton-driven enhanced nanoconverter (PEN) that selectively accumulates in tumor regions and re-establishes the tumor microenvironment by depleting glucose, suppressing heat shock proteins, and promoting the activation of PANI. PEN can differentiate normal and cancerous tissues bidirectionally to minimize adverse effects, and achieves tumor elimination with high specificity through mild hyperthermia/immune response. PEN-induced adaptive antitumor immunity is effective for eliminating distant tumors and suppressing tumor metastasis and recurrence.