摘要The Wnt/β-catenin signaling pathway is renowned for its contribution to the immunosuppressive microenvironment in non-small cell lung cancer(NSCLC).Consequently,inhibiting this pathway has emerged as a promising strategy to enhance immune activation and reinstate T cell responses in cancer treatment.In this study,we initially investigate the metabolic characteristics of Wnt-hyperactivated NSCLC using mass spectroscopic detection in a mouse in-situ model and unveil its significant feature of acid accumulation at tumor sites.Building upon this discovery,we design an acid-sensitive peptide-carnosic acid(CA)supramolecular droplet(Pep1@CA),which leverages the acidic microenvironment characteristic of NSCLC for controlled release.By doing so,we aim to enhance targeting efficiency while minimizing off-target effects.As anticipated,Pep1@CA demonstrates potent tumor-specific inhibition of the Wnt signaling pathway and effectively reactivates T cell immunity in Wnt-hyperactivated NSCLC.Importantly,comprehensive in vivo evaluations reveal significant antitumor efficacy alongside excellent biosafety profiles.Collectively,this study provides a therapeutic strategy with promising clinical trans-lational potential for targeting the Wnt signaling pathway and offers theoretical support for its appli-cation in immunotherapy.This innovative approach underscores that targeting pathways beyond traditional immunotherapy can also activate tumor immunity,thereby expanding the potential of cancer immunotherapy.