• • The hydrogel achieves lesion-specific adhesion via DNA base pairing, with LFUS anchoring complementary oligonucleotides; this precision targeting minimizes collateral damage to healthy tissue, a critical improvement over generic adhesive hydrogels.
• • Under HFUS, Ce6 generates substantial reactive oxygen species, triggering mtDNA release; concurrent HFUS accelerates Mn2+ release, potentiating cGAS-STING activation. This dual-action mechanism enhances immunotherapy efficacy, as evidenced by dendritic cell maturation and cytotoxic T lymphocyte priming.
• • The cGAS-STING pathway activation is Mn2+-dependent, with Mn2+ enhancing sensitivity to dsDNA (as per reference 67). This synergy between sonodynamic therapy and STING agonism offers a potent approach to reverse immunosuppression in OLK.
• • The therapy induces immunological memory, which is crucial for preventing OLK recurrence and malignant transformation, addressing a key clinical unmet need in premalignant lesion management.