Glutathione-Responsive Metal–Organic-Framework-Derived Mn x O y /(A/R)TiO 2 Nanoparticles for Enhanced Synergistic Sonodynamic/Chemodynamic/Immunotherapy

作者：Yilin Yang, Ning Wang, Zhihua Wang, Fei Yan, Zhan Shi, Shouhua Feng · 发表于：ACS Nano · 年份：2025 · DOI：10.1021/acsnano.4c12304 · 被引用次数：36 · 研究领域：Nanoplatforms for cancer theranostics、Nanoparticle-Based Drug Delivery、Advanced Nanomaterials in Catalysis

Despite the potential of sonodynamic therapy (SDT) in treating malignant tumors, the lack of effective sonosensitizers has limited its clinical implementation. In this study, we explored the relationship between the heteroatom doping concentration in metal–organic frameworks and interface formation after pyrolysis by regulating the addition of manganese sources and successfully derived Z-scheme heterojunctions Mn x O y /(A/R)TiO 2 (MTO) in situ from MIL-125-NH 2 (Ti/Mn). The electron transfer pathway introduced by interfacial contact promoted carrier separation and greatly preserved the effective redox components, significantly influencing the performance of reactive oxygen species generation. Upon reaching the tumor sites, MTO effectively depleted glutathione to alleviate the suppressive tumor environment, and the heterojunctions and Mn x O y in MTO facilitated SDT and synergistic chemodynamic therapy (CDT), respectively, leading to enhanced immunogenic cell death (ICD). Furthermore, Mn 2+ uptake by dendritic cells (DCs) and the tumor-associated antigens released due to ICD activated the stimulator of interferon genes pathway, which elicited a robust tumor-specific immune response by driving the maturation of DCs and the activation of T cells. In addition, the activated T cells secreted high levels of interferon-γ to enhance Mn 3+ /Mn 2+ -mediated ferroptosis in metastatic tumor cells. The combination of MTO-mediated synergistic therapy and PD-L1 checkpoint blockade exhibite...