Tan Yong, He Huihui, Yin Baoli, Lu Dingyou, Li Jinyu, Shen Hengxin, Zhang Xiao-Bing, Fang Yu, Song Guosheng
State Key Laboratory of Chemo and Biosensing, College of Chemistry and Chemical Engineering, Hunan University, Changsha, Hunan, 410082, China.
Angew Chem Int Ed Engl. 2025 Jul;64(29):e202507180. doi: 10.1002/anie.202507180. Epub 2025 May 20.
Sonodynamic therapy (SDT) has emerged as a promising non-invasive approach for immunotherapy. However, its broad applicability is often limited by the inefficiency of sonosensitizers. Here, we introduce a novel series of porous coordination cages (PCCs) specifically engineered to enhance sonodynamic therapeutic performance for the first time. These PCCs incorporate energy harvesting and conversion components, with variations in bandgap, electrical conductivity, and redox activity. Characterized by atomically precise compositions and well-defined structures, the PCCs enable strategic manipulation of functionalized moieties and metal centers, allowing for precise control over their sonodynamic efficiency. Their small particle size enhances penetration through dense tumor extracellular matrices, significantly improving tumor permeability. Upon ultrasound stimulation, the PCCs exhibit robust sonodynamic effects, resulting in increased reactive oxygen species (ROS) levels in tumor cells, which triggers apoptosis and antigens release. Notably, PCC-1 demonstrates metal-mediated catalytic activity, converting endogenous hydrogen peroxide into additional ROS, synergistically enhancing SDT efficacy and activating the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway in dendritic cells. In tumor model, PCCs effectively inhibited tumor growth and activated immune responses both locally and systemically. Collectively, these findings underscore the exceptional sonodynamic-immunotherapeutic potential of PCCs, paving the way for innovative strategies in tumor treatment.
声动力疗法（SDT）已成为一种有前景的非侵入性免疫治疗方法。然而，其广泛应用常常受到声敏剂效率低下的限制。在此，我们首次引入了一系列专门设计的新型多孔配位笼（PCCs），以增强声动力治疗性能。这些PCCs包含能量收集和转换组件，在带隙、电导率和氧化还原活性方面存在差异。PCCs具有原子精确的组成和明确的结构，能够对功能化部分和金属中心进行策略性操作，从而精确控制其声动力效率。它们的小粒径增强了穿过致密肿瘤细胞外基质的穿透能力，显著提高了肿瘤渗透性。在超声刺激下，PCCs表现出强大的声动力效应，导致肿瘤细胞中活性氧（ROS）水平升高，进而触发细胞凋亡和抗原释放。值得注意的是，PCC-1表现出金属介导的催化活性，将内源性过氧化氢转化为额外的ROS，协同增强SDT疗效，并激活树突状细胞中的环磷酸鸟苷-腺苷酸合酶-干扰素基因刺激物（cGAS-STING）途径。在肿瘤模型中，PCCs有效地抑制了肿瘤生长，并在局部和全身激活了免疫反应。总的来说，这些发现强调了PCCs卓越的声动力免疫治疗潜力，为肿瘤治疗的创新策略铺平了道路。
