Semiquinone Radical‐Engineered Nanoparticles for Hypoxia‐Adaptive and InflammationControlled Microwave‐Immunotherapy of Liver Tumor

作者：Meizhen Zhou, Jing Zhu, Dongyun Zhang, Jianping Dou, Wenqi Chen, Yi Zhang, Xiaopeng Gao, Jixi Zhang, Ping Liang, Jie Yu · 发表于：Advanced Healthcare Materials · 年份：2025 · DOI：10.1002/adhm.202503568 · 被引用次数：1 · 研究领域：Nanoplatforms for cancer theranostics、Sulfur Compounds in Biology、Advanced Nanomaterials in Catalysis

Abstract Reactive Oxygen Species (ROS) exhibit a paradoxical dual role in tumor therapy. Tumor hypoxia restricts therapeutic ROS generation, while excessive secondary ROS post‐ablation suppresses T‐cell function yet promotes M1 macrophage polarization. Semiquinone radical‐doped reduced polydopamine nanoparticles (PDA red ) loaded is developed with resiquimod (R848) (PDA red @R848) via π–π stacking. Reduction enriches the nanoparticles with semiquinone radicals, enhancing dielectric properties and dipole polarization under electromagnetic effects. This nanoparticle enables the specific hydrogen radicals (H•)/ROS generation in oxygen‐heterogeneous tumor under microwave irradiation. In microwave dynamics therapy (MDT) phase, PDA red converts protons (H⁺) to H• under microwave irradiation in hypoxic regions, targeting cytochrome c and inducing tumor cell apoptosis and immunogenic cell death; PDA red establishes an internal electric field under microwave, facilitating electron–hole separation to produce ROS and trigger ferroptosis in normoxic regions. In post‐MDT phase, PDA red ’s intrinsic polyphenols scavenge excess secondary ROS produced by damaged cells, alleviating immunosuppression. Compared with blank control, PDA red @R848 increased CD4⁺/CD8⁺ T‐cell infiltration (6.4‐fold) and M1 macrophage polarization (2.5‐fold M1/M2 ratio elevation). Pro‐inflammatory cytokines are significantly reduced, and tumor volume is suppressed by 94.8%. This study proposes an innovative dual‐acti...